Higher Hematologic Toxicity Research Articles

The efficacy and safety of conversion therapy after initial systemic chemotherapy in advanced esophageal cancer with distant metastases: A multicenter retrospective observational study.

310 Background: Systemic chemotherapy, with or without radiation, has been the standard treatment for esophageal squamous cell carcinoma (ESCC) with distant metastasis. The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable ESCC after initial treatment. In the present study, we examined the safety and effectiveness of conversion therapy for ESCC. Methods: Conversion therapy was defined as surgery or chemoradiation therapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. The patients who underwent conversion therapy for ESCC between 2011 and 2021 at participating institutions were retrospectively reviewed. Patient backgrounds, treatment outcomes, and overall survival (OS) were evaluated. Results: From 22 institutions, 149 patients were enrolled. As defined, all patients received systemic chemotherapy as an initial treatment. The distant metastatic sites in para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial treatment, 116 patients underwent surgery and 33 patients received CRT as conversion therapy. Of 116 patients who underwent conversion surgery, the incidence rate of postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%, respectively. R0 resection was obtained in 87%. Regarding the non-hematological toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hematologic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p = 0.112). Pathological responders showed a significantly longer OS than non-responders (3y-OS, 56.4% vs 36.1%, p = 0.010). The distribution or number of distant metastases were not identified as prognostic factors. Conclusions: This study showed that conversion therapy for ESCC patients with distant metastasis could be conducted safely and have a favorable prognosis. Since its survival benefit would depend on the pathological response, it is important to develop an indicator to predict pathological response before surgery and carefully select appropriate candidates of conversion therapy in ESCC.

Single Center Retrospective Study of Midostaurin Plus Intensive Chemotherapy for Older Patients with Newly Diagnosed FLT-3 Mutated Acute Myelogenous Leukemia

Background: Mutations in FLT3 (FLT3m), either internal tandem duplication (ITD) or tyrosine kinase domain (TKD) are found in approximately 25% of AML patients. The current standard of care for eligible patients is induction chemotherapy with 7 + 3 regimen with the addition of multikinase inhibitor midostaurin, based on CALGB 10603 which enrolled patients up to 59 years of age (Stone et al; NEJM 2017). Quizartinib recently demonstrated improved overall survival (OS) compared to placebo when combined with standard 7+3 induction in patients up to 75 years of age, although the benefit in patients 60 and above was less clear (Erba et al; Lancet Oncol 2023). We sought to review the clinical outcomes among patients 60 years of age or greater at our institution for who received midostaurin with 7+3 for newly diagnosed (ND) FLT3m AML. Methods: We retrospectively reviewed 20 patients, 60 years of age or older who received midostaurin in combination with 7+3 (7+3+Mido) for the treatment of ND-FLT3m AML. Response criteria of CR (complete remission) and CR without hematological recovery (CRi) were defined per standard International Working Group (IWG) AML response criteria. The primary endpoint was defined as composite CR rate (cCR: defined as patients achieving CR +CRi). Minimal residual disease (MRD) assessment was done on post-induction bone marrow aspirate using multiparametric flow cytometric assessment. The secondary endpoints were OS, leukemia-free survival (LFS) among patients with CR/Cri and proportion of patients who underwent subsequent allogeneic hematopoietic cell transplant (alloHCT). Results: Patients' demographic, cytogenetic and molecular features are summarized in Table 1, briefly, the median age was 64 (range 61-75), males (n=12, 60%), de novo AML (n=19, 95%), FLT3 ITD (n=13, 65%), FLT3 TKD (n=7, 35%). The most common consolidation regimen was high dose cytarabine (HiDAC) in combination with midostaurin (n=5, 25%). Grade 3 or higher hematologic toxicity was uniformly seen and the most common grade 3 or higher non-hematologic toxicities were neutropenic fever (19/20; 95%), cardiac disorders (3/20; 15%), and diarrhea (3/20; 15%). Dose reductions/interruption of midostaurin was required in 35% patients (n=7) and one patient died due to induction related mortality. 7+3+Mido yielded an overall response rate of 90% (18/20), with cCR noted in 75% (15/20) and MLFS seen in 15% (3/20) patients. MRD negative remission was documented in 40% (6/15) patients treated (table 2). The median follow up for the entire cohort was 9.3 months and overall survival at 6 months was 70% (14/20). The majority of patients, 70% (14/20) subsequently underwent alloHCT from matched or haploidentical donor. Reduced intensity conditioning (n=12/14; 86%) and GVHD prophylaxis with tacrolimus/ sirolimus prophylaxis (n=8; 57%) was commonly used in patients undergoing alloHCT. Six patients did not proceed to alloHCT due to death (n=4, one each due to sepsis, disease progression, infection, or intracranial bleed), comorbid conditions (n=1) or short follow up. The median OS for non HCT group was 2.3 months (range: 0.6-6.5). Detailed HCT outcomes data was available subset of patients at last data cut off (9/14; 65%). The Median age of patients undergoing HCT was 65 years (range: 62-76). The median KPS and HCT-CI for these patients was 90% (range :80-90%) and 1.5(range: 0-5) respectively. The majority of patients underwent alloHCT in CR-1(90%), all using PBSC graft from donor. The median duration of follow-up from transplant to last contact or death in the nine evaluable patients was 12.1 months. Median OS and leukemia free survival was not reached and 1-year GRFS was 50% (range:14-79%). Five patients (36%) patients received post-transplant FLT3 maintenance with the most common agents being midostaurin (n=2) and gilteritinib (n=2). Conclusion: The addition of midostaurin to intensive 7+3 chemotherapy induction for ND FLT3m AML is feasible and well tolerated in older AML patients. The combination results in high remission rates and the majority of patients are able to proceed to alloHCT.

High-dose (60 Gy) intensity-modulated radiotherapy with concurrent weekly cisplatin followed by intracavitary radiation in locally advanced cervical cancer: A phase II prospective clinical trial

ObjectiveRadiotherapy dose-escalation using intensity-modulated radiotherapy (IMRT) has been necessary to improve treatment results in cervical cancer. MethodsThis was a phase II prospective clinical trial. 88 patients with FIGO II-IVa cervical cancer were enrolled in a single center. They received high-dose (60 Gy) IMRT with weekly cisplatin to the primary tumor and clinically positive nodes followed by intracavitary radiation. The primary endpoint was 30-month PFS rate (Target; 82%, an increase of 20% compared to GOG 120 trial using standard-dose radiotherapy). Secondary endpoints were tumor response, toxicity, recurrence, distant metastasis, and overall survival. ResultsProgression-free survival rate at 30 months was 82.8%. Overall survival, locoregional recurrence, distant metastasis, and para-aortic recurrence rates at 30 months were 93.6%, 8.2%, 9.2%, and 2.4%, respectively. Forty-five (51.1%) of 88 patients achieved downstaging on MRI during radiotherapy and 80 (90.9%) patients had clinically complete response at three months after high-dose IMRT and intracavitary radiotherapy. The 30-month recurrence-free survival (92.9% vs. 73.1%, P = 0.009) and overall survival (100% vs. 87.0%, P = 0.006) were significantly higher in the downstaged group than in the non-downstaged group during radiotherapy. Grade 3 or higher hematologic toxicity was found in 11 (12.5%) patients and grade 3 or higher non-hematologic toxicity was found in 3 (3.4%) patients. Fourteen had chronic urinary (8.0%), intestinal (5.7%) toxicity, pelvic insufficiency fracture (2.3%) or vesicovaginal fistula (2.3%). ConclusionHigh-dose (60 Gy) IMRT with concurrent weekly cisplatin in locally advanced cervical cancer yielded favorable progression-free survival outcome. Tumor response during radiotherapy can be a significant prognostic factor for PFS.Clinical trial information: This prospective trial is registered at ClinicalTrials.gov Identifier: NCT02993653.

Impact of radiation on immune cells in patients with low-grade brain tumor: Identifying critical factors affecting lymphopenia and neutrophil-to-lymphocyte ratio.

Studies about the effect of radiation therapy (RT) on immune cells are usually limited to a high-grade glioma mostly exposed to chemotherapy and a high dose of steroid which also could affect immune cells. The purpose of this retrospective analysis of low-grade brain tumor patients treated by RT alone is to determine significant factors influencing neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC). A total of 41 patients who received RT between 2007 and 2020 were analyzed. Patients who received chemotherapy and high-dose of steroid were excluded. ANC and ALC were collected before starting RT (baseline) and within one-week before ending RT (post-treatment). Changes of ANC, ALC, and NLR between baseline and post-treatment were calculated. ALC decreased in 32 patients (78.1%). NLR increased in 31 patients (75.6%). No patients developed grade 2 or higher hematologic toxicities. The decrease of ALC was significantly correlated with the dose to brain V15 in a simple and multiple linear regression (p = 0.043). Brain V10 and V20 adjacent to V15 were also marginally significant factors determining the reduction of lymphocytes (p = 0.050 and p = 0.059, respectively). However, it was difficult to find predictive factors affecting changes of ANC and NLR. In low-grade brain tumor patients who are treated by RT alone, ALC decreased and NLR increased in three-fourth of patients, although the magnitude was minimal. The decrease of ALC was mainly affected by low dose to the brain. However, RT dose was not correlated with changes of ANC or NLR.

Phase 2 study of weekly polymeric micelle-formulated paclitaxel plus gemcitabine in patients with recurrent and metastatic adenocarcinoma of the pancreas.

e16257 Background: Cremophor EL(CrEL), used to enhance drug solubility, may add paclitaxel’s toxicities such as hypersensitivity reactions or peripheral neuropathy. The rationale for developing an alternative paclitaxel formulation concerns CrEL-related side effects, and a novel paclitaxel delivery system might augment its therapeutic efficacy. GENEXOL-PM (GPM) is a novel polymeric micelle formulated paclitaxel free of CrEL. This is to report the efficacy and safety of the weekly combined chemotherapy with GPM and gemcitabine in patients with recurrent and metastatic adenocarcinoma of the pancreas conducted in multicenter, Republic of Korea. Methods: This was a multicenter, phase 2 study of weekly GENEXOL-PM plus gemcitabine in subjects with recurrent and metastatic adenocarcinoma of the pancreas. The patients who had met the inclusion/exclusion criteria were enrolled and received GPM (125 mg/m2) and gemcitabine (1000 mg/m2) intravenously on day 1, 8, and 15 in every 4 weeks, unless definite disease progression was confirmed. Tumor evaluation was conducted at the end of every 2 cycles according to Response Evaluation Criteria in Solid Tumors (RECIST). Pre-planned test and adverse reaction evaluation were managed after each cycle of drug administration and before the next cycle. The primary end point of this study was objective response rate, and the secondary end points were toxicity, progression free survival and overall survival. Results: Between January 2016 and February 2022, total 32 patients were enrolled; median age was 65 years; male (n=16) and female (n=16). 26 patients were assessable for efficacy. Overall response rate was 19.2% (5/26 patients) and clinical benefit rate (partial response + stable disease) was 34.6% (9/26 patients). The median progression-free survival and overall survival were 8 months, 22 months, respectively. The median number of cycles administered was 5.0 (range=1-21). Most common grade 3 or higher hematological toxicities were: neutropenia occurred in 9 patients (29.0%), neutrophil count decrease 5 patients (16.1%) and anemia 5 patients (16.1%). The most common grade 3/4 non-hematological toxicities were generalized muscle weakness 3 patients (11.5%), pneumonitis 3 patients (11.5%) and liver abscess 2 patients (4.3%). Conclusions: Treatment of advanced pancreatic cancer with combination of GENEXOL-PM and gemcitabine was generally well tolerated and showed a favorable toxicity profile. In this study, efficacy results of combination regimen were comparable to that observed historically with albumin-bound paclitaxel and gemcitabine combination. This regimen demonstrated chemotherapeutic effects to warrant further development when used as first-line chemotherapy for advanced pancreatic cancer. Future studies directly comparing GENEXOL-PM and albumin-bound paclitaxel are required. Clinical trial information: NCT02739633 .

Bone Marrow Toxicity and Tolerance of Sandwich Therapy for Advanced-Stage Endometrial Cancer: A Single-Institution Experience

<h3>Purpose/Objective(s)</h3> Adjuvant therapy for advanced-stage endometrial cancer (EC) involve chemotherapy (CT) and/or radiation therapy (RT). Institutional practices vary regarding the sequencing of these therapies. While recent trials favored concurrent chemoradiation followed by consolidating CT, there is no randomized comparison of efficacy between ‘sandwich' (ST) versus concurrent CT. Previous studies show BM dose is predictive of hematological toxicities (HT) in concurrent chemoradiation. In this study, we sought to determine whether bone marrow dose contributes to hematological toxicity in ST for treatment of advanced-stage EC. <h3>Materials/Methods</h3> Data for patients who received ST (CT with carboplatin/paclitaxel then 45 Gy external beam radiation therapy [EBRT] with/without paraaortic [PA] fields then additional CT) at a single academic institution for EC cases was abstracted. Full ST was defined as 3 CT cycles, then RT, followed by a final 3 CT cycles. Grade 3 (G3) higher hematologic toxicities (ANC <1000, Hgb <8.0, platelet count <50,000) were recorded for each patient based at the time of infusion or radiation therapy. T-test and Chi-square test were used as appropriate to determine association. <h3>Results</h3> 98 EC patients that underwent ST were included; 66.0% were stage IIIC. 84% of patients completed full ST, and 26.3% of cases experienced ≥1 treatment delay. Among cycle delays cases, 57.7% had ≥1 G3 hematologic toxicity: 10 neutropenia, 4 anemia, and 3 thrombocytopenia. HT rate was 49.0%: 34% neutropenia, 13% anemia, 12% thrombocytopenia. Frequency of cycle delay (31.3% vs. 21.6%) or ST non-completion (13.7% vs. 18.4%) were not significantly associated with HT presence (p>0.05, all). Significantly fewer patients who had HT both pre- and post-EBRT completed post-sandwich CT compared to toxicities occurring at other time intervals (Table). While patients with ≥2 HT during their treatment received a significant larger mean bone marrow radiation dose (69.0 vs 72.5%, p=0.037), overall dosimetric data were similar regardless of HT timing during treatment. PA boost did display more frequent HT following RT (21.1% vs. 51.7%, p = 0.033) but completed ST at similar rates (63.2% vs 36.8%, p=0.441). There was a 10% mortality rate; overall survival was similar despite presence of HT occurrence, or with HT requiring a cycle delay or cycle non-completion (p>0.05, all cases). <h3>Conclusion</h3> In our study, BM dose does matter in determining HT even in ST, but does not affect overall treatment completion. The treatment completion rate is comparable to those reported historically for CT only arm. Low rates of cycle interruption and similar overall survival point to a promising safety and efficacy profile with ST.

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results

Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers (NCT03874897). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 108, 3.75 × 108 or 5.0 × 108 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.

Association between body composition and chemotherapy‐related toxicity in children with lymphoma and rhabdomyosarcoma

Body composition is associated with chemotherapy toxicity (chemotoxicity) in adults with cancer; this association remains unexplored in children with cancer. Using baseline computed tomography scans of 107 children with Hodgkin lymphoma (n = 45), non-Hodgkin lymphoma (n = 42), or rhabdomyosarcoma (n = 20), this study examined body composition (skeletal muscle index [SMI], skeletal muscle density [SMD], and height-adjusted total adipose tissue [hTAT]) to determine its association with chemotoxicity. Clinical characteristics and chemotoxicities were abstracted from medical records. Primary outcomes included grade 4 or higher hematologic toxicities and grade 3 or higher nonhematologic toxicities within 6 months of the diagnosis. Logistic regression models accounting for repeated measures were constructed to examine the association between body composition indices and chemotoxicities; adjustments were made for age at diagnosis, sex, race/ethnicity, cancer type, risk group, body mass index (measured as a percentile), or body surface area. The median SMI was 41.0 cm2 /m2 (range, 25.8-68.6 cm2 /m2 ), the median SMD was 54.1 HU (range, 35-69.4 HU), and the median hTAT was 19.5 cm2 /m2 (range, 0-226.7 cm2 /m2 ). Grade 4 or higher hematologic toxicities and grade 3 or higher nonhematologic toxicities were observed in 74.7% and 66.3% of the chemotherapy cycles, respectively. A higher SMD at diagnosis was associated with lower odds of grade 4 or higher hematologic toxicity (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.85-0.97; P = .004). SMI (OR, 0.99; 95% CI, 0.95-1.04; P = .7) and hTAT (OR, 1.00; 95% CI, 0.99-1.01; P = .9) were not associated with hematologic toxicities. Nonhematologic toxicities did not show any association with body composition. The association between low SMD and hematologic toxicities in children with lymphoma or rhabdomyosarcoma could be due to body composition-based biodistribution of chemotherapeutic agents and needs further investigation. Body composition at cancer diagnosis in children with lymphoma and rhabdomyosarcoma may provide information that could identify those at risk for serious side effects from chemotherapy. Routinely used measures such as body mass index and body surface area show poor correlations with body composition assessed via computed tomography scans.

Bispecific T-Cell Engager Antibodies in Multiple Myeloma- a Systematic Review of Phase 1 Clinical Trials

IntroductionOne of the emerging targeted strategies for treatment of multiple myeloma (MM) is the use of robust immune responses via T cell activation against tumor cells. B-Cell Maturation Antigen (BCMA), a cell surface protein, remains a potential target for therapeutic interventions. Recently, bispecific T cell engager therapy, targeting BCMA and CD3 antigens on plasma and T cells respectively, have shown promising results in preclinical and early clinical studies in the context of relapsed/refractory myeloma (RRMM). We conducted a systematic review of phase 1 trials to report the efficacy and safety of Bispecific T-Cell Engager antibodies for MM.Methodology:We systematically searched multiple databases, including PubMed, Embase, Cochrane, and Clinicaltrials.gov. We also searched major conferences for oral or poster presentations. MeSH terms and keywords for MM and bispecific antibodies were utilized. We included all original studies reported in English language published from 1990 until June 2021. The primary database search yielded 390 articles. After excluding review articles, duplicates, irrelevant articles, and non-human studies, six phase 1 clinical trials were included to evaluate the efficacy and safety outcomes.Results:A total of 253 patients were identified from the six phase 1 studies, among whom 247 were evaluable for response, while the safely analysis involved all the patients. A study conducted by Krishan et al. (n= 40) stated an overall response rate (ORR) of 65% among patients receiving subcutaneous (SQ) teclistamab with a median of five prior therapies, 30% and 58% of the responders had a complete response (CR) and very good partial response (VGPR), respectively. A similar ORR of 63% was reported in 28 patients with a median of 5.5 prior therapies receiving SQ talquetamab by Berdeja et al. Cohen et al reported an ORR of 51.7% in patients receiving IV BFCR4350A at doses ≥3.6/20mg (Partial response (PR):17.2% and CR: 10.3%). SQ elranatamab achieved an ORR of 75% in 17 patients who received doses ≥215 μg/kg. Madduri et al. evaluated REGN5458 monotherapy with dose escalation from 3 to 96 mg among 45 patients and reported an ORR of 60% at the highest dose levels. ORR of 31% was reported in 42 patients receiving IV BI836909/AMG 420 by Topp et al. The median time to response (TTP) was 1 month in the majority of the studies. (Table 1)The most common grade three or higher hematological toxicities were neutropenia and anemia, while among non-hematological toxicities, infections were the most common. The incidence of cytokine release syndrome and neurotoxicity varied from 24% to 74% and 2 % to 20%, respectively. (Table 3)Conclusion:The early clinical data of Bispecific T-Cell Engager therapy in heavily pretreated RRMM patients shows promising results regarding its efficacy and safety profile. It represents a whole new horizon of targeted approach towards RRMM. Phase II / III studies are being conducted to evaluate this potential treatment approach in patients with MM. [Display omitted] DisclosuresAnwer: GlaxoSmithKline: Research Funding; BMS / Celgene: Honoraria, Research Funding; Allogene Therapeutics: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding.

Prospective Evaluation of Acute Toxicities in Postoperative Patients of Glioblastoma Treated With Adjuvant Hypofractionated Radiotherapy (60 Gray in 20 Fractions)

<h3>Purpose/Objective(s)</h3> The current standard of care for post operated patients of glioblastoma (PO-GBM) is adjuvant radiotherapy with concurrent and adjuvant temozolomide (RT-TMZ). Accelerated tumor repopulation due to increased overall treatment time could be responsible for radio resistance and poorer outcomes. The role of hypofractionated adjuvant radiotherapy (HYPO-RT) has been evaluated in elderly patients but is unknown in other subsets of age group. We aim to evaluate prospectively the safety and tolerability of HYPO-RT with concurrent and adjuvant temozolomide in PO-GBM patients. <h3>Materials/Methods</h3> Between December 2019 to December 2020, we enrolled 15 PO-GBM patients in a prospective ethic approved institutional study (IEC No. 53/19). Computed- tomography based planning with aid of contrast enhanced pre-operative MRI fusion was done. All patient received HYPO-RT 60 Gray in 20 fractions at 3 Gy per fraction over 4 weeks with concurrent Temozolomide 75 mg/m² with 3D-conformal radiotherapy technique. 45 Gray in 15 fractions were delivered in phase 1 followed by a phase 2 boost of 15 Gray in 5 fractions. Toxicity assessment was done according to common terminology criteria for adverse events 5.0. Memory impairment and cognitive dysfunction were assessed with mini mental status examination (MMSE). <h3>Results</h3> All patients completed the full course of radiotherapy without any interruption with median radiotherapy treatment time of 4 weeks (4-5 weeks). Median age was 52 years (20-65), median Karnofsky performance score was 70 (range 70-90) with M: F ratio of 10:5. 4 (27%) and 11 (73%) patients were RTOG-RPA class IV and class V respectively. 5 (33%) patients underwent gross total resection, 9 (60%) underwent subtotal resection and 1 (7%) patient had biopsy only. IDH-wild type was reported in 4 patients. Median follow was 5 months (range 3-10 months). No patient reported grade 2 or higher hematological toxicity during RT. None of the patient showed grade 3 or 4 non-hematological toxicity. 11 (73%) patients have grade 1 and 4 (26%) patients had grade 2 cognitive dysfunction. Six (40%) patients had grade 1 and 2 (13%) had grade 2 headache. Only 1 (6.6%) patient showed depressed level of consciousness and there was no reported episode of seizure. 11 (73%) patients had grade 1 and 1 (6.6%) patient showed grade 2 memory impairment. At the time of last follow up; 8 patients have completed adjuvant TMZ, 4 patients are on adjuvant TMZ and 3 patients have died. <h3>Conclusion</h3> Adjuvant HYPO-RT with RT-TMZ is well tolerated in terms of acute toxicity and may be a good alternative to reduce overall treatment time and counteract tumor repopulation in PO- GBM. Further follow up of our study cohort will elucidate the clinical outcome of patients treated with this HYPO-RT approach.

823 INDUCTION CHEMOTHERAPY WITH 2-WEEKLY DCF REGIMEN FOR SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS

Abstract Tri or 4-weekly Decetaxel, Cisplatin and Fluorouracil (DCF) regimen for esophageal squamous cell carcinoma (ESCC) was reported to be highly effective as a neoadjuvant chemotherapy, however higher hematologic toxicity rate was problematic with this regimen. JCOG0807 study revealed 2-weekly DCF regimen was less toxic and effective for unresectable or metastatic ESCC, however its efficacy for resectable ESCC as an induction chemotherapy is unknown. Methods The aim of this study was to clarify the safety and efficacy of 2-weekly DCF regimen for resectable ESCC. We reviewed 94 pts with ESCC who received 2-weekly DCF regimen (30 mg/m2 docetaxel on days 1 and 15, 80 mg/m2 cisplatin on day 1, 800 mg/m2 fluorouracil on days 1–5, repeated every 3 weeks) between Apr. 2010 and Dec. 2019. Clinical stage II, III, IVA and IVB ESCC pts were included. Those with cT4b and cM1 other than No.104 nodes were excluded. The safety, efficacy and survival were retrospectively investigated. Results Fifty-eight pts were enrolled. Clinical stage was II in 6, III in 39, IVA in 6 and IVB in 7. Common grade 3/4 adverse events were neutropenia (19%), hyperglycemia (7%), and febrile neutropenia (3%). Treatment related death was occurred in one (2%) for neutropenia. The overall response rate (RR) was 50% and disease control rate was 93%. The R0 resection rate was 81% without in-hospital deaths. Grade 2/3 pathological RR was 38% and pCR rate was 7%. Median survival time (MST) was 84 mts and 5-yr OS was 59% with a median observational period of 37 mts. Conclusion The 2-weekly DCF regimen for resectable ESCC showed tolerable hematologic toxicity, relatively better efficacy and survival. This regimen can be an alternative choice as an induction chemotherapy for ESCC.

Prephase rituximab/prednisone therapy and aging-related, proinflammatory cytokine milieu in older, vulnerable patients with newly diagnosed diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) predominantly affects older adults with suboptimal therapeutic outcomes due to increased treatment-related mortality and toxicities in vulnerable patients, clinically defined by geriatric impairments such as functional limitation, multimorbidity, or cognitive deficits. In this prospective pilot study, we evaluated a rituximab/prednisone prephase treatment strategy in 33 older, vulnerable patients with newly diagnosed DLBCL, defined by either age ≥70 years or age 60-70 years with Karnofsky performance scale (KPS) <80. A single dose of rituximab 375 mg/m2 between 3-10 days and oral prednisone for at least 5 days prior to the first dose of chemoimmunotherapy was administered. All patients completed prephase treatment and all but one commenced anthracycline-based chemoimmunotherapy. Only one early cycle death occurred. Toxicity events, defined by either unplanned hospitalization, unplanned dose reduction/delay, or chemotherapy discontinuation, occurred in 22 patients (67%). Sixteen patients (48%) experienced grade 3 or higher non-hematologic toxicities and/or grade 4 or higher hematologic toxicities. With a median follow-up of 4.4 years, both 5-year progression-free survival and overall survival were at 81% (95% confidence interval: 69-96). Importantly, we found that phenotypic impairments in basic and instrumental activities of daily living, physical function, mobility, KPS, and Cancer and Aging Research Group chemotherapy toxicity risk score were significantly associated with senescence-associated, proinflammatory cytokine milieu which was readily reversed with prephase treatment, potentially explaining its clinical effectiveness. Prephase therapy with rituximab/prednisone should be considered for all older, vulnerable DLBCL patients prior to curative intent, anthracycline-based chemoimmunotherapy. This trial was registered as clinicaltrials gov. Identifier: NCT 89028394.

Impact of a Brief Touchscreen Based Modified Geriatric Assessment on the Care of Older Adults with Multiple Myeloma

Background: Most adults (60%) diagnosed with Multiple Myeloma (MM) are > 65 years old (YO) and thus are at higher risk for toxicities of cancer treatment. Geriatric assessment (GA) can identify patients at risk for toxicity and morbidity more effectively than age or performance status, but is not easily integrated into a busy clinical setting. A technology assisted, modified GA (mGA) that includes the Palumbo frailty score can be used to summarize and report relevant clinical and self-reported symptom data to inform treatment decision making.Methods: A prospective, single arm multisite study is underway with MM patients >65 YO to test feasibility, usability, and acceptability of a technology based mGA in a busy clinic. Patients needing a new treatment complete a tablet based survey that includes 28 items comprising the Charlson Comorbidity Index (CCI), Katz Activity of Daily Living (ADL) Score and Lawton Instrumental ADL (IADL) Score prior to meeting with the provider. Additional clinical information such as Creatinine Clearance (CrCl) is added by staff. The composite frailty index (FI) and items influencing the score are provided on a physician facing dashboard at the patient/provider visit. The provider reviews the mGA results with the patient and treatment is selected.Results: To date, 118 of 210 patients have enrolled. Most participants are white (72%, n=86); mean age is 72 (range 65-85). Patients are satisfied with the computer program overall (84% indicated they are satisfied or very satisfied with the overall program), satisfied with the ease of use (91% were satisfied or very satisfied), and feel others can use the program easily (90% agreed or strongly agree others would learn to use the program quickly). Patients complete the survey in an average of 7.71 minutes (range 2-17) and providers report an average of 3.2 minutes (range 1-10) to review the mGA results. Patients were fit (38%, n=45), intermediate fit (31%, n=37) or frail (31%, n=36), and the fit/frailty status informed treatment decisions. Providers selected treatments that were more aggressive (increased dose or dose intensity) for the fit patients while frail patients received milder treatments evidenced by a reduced number of agents, regimens with less toxicity, or a different route of administration (χ2 =20.02, p<.0001). There was also a significant correlation of patients considered to be transplant eligible with fit status and patients considered not transplant eligible with frail status (p=.004). There is a trend toward frail patients having more dose modifications during the 3 months follow up period (p=.09). The mGA information with greatest impact on provider treatment decisions was: fit/frailty status or the rationale for the summary score (67%, n=100), creatinine clearance (17%, n=25), peripheral neuropathy (6%, n=9) and falls (3%, n=4). Outcomes on the first 18 patients at three months post treatment decision visit show 33% had grade 3 or higher hematologic toxicities, 66% had dose modifications over the three-month study period, and 33% had therapy discontinued earlier than planned.Conclusion: The limited additional time required by patients to complete the survey and-the provider to review the mGA results together with the high rate of patient satisfaction shows a mGA can be easily incorporated into clinical workflow. Real time scoring of assessment items into a composite score indicating fit/frailty status influenced treatment decisions at the point of care to allow aggressive treatment of fit patients and modifications to decrease toxicity in frail patients. Final study results will report patient outcomes at three months post intervention visit correlated with fit/frailty status. DisclosuresMohile:Seattle Genetics: Consultancy. Wildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy. Wujcik:Carevive Systems Inc: Employment. Davis:Carevive Systems Inc: Employment. Digiovanni:Carevive Systems Inc: Employment. Stricker:Carevive Systems Inc: Employment, Equity Ownership.

Thalidomide and Dexamethasone Maintenance after Autologous Stem Cell Transplantation in Newly Diagnosed Korean Multiple Myeloma Patients: A Prospective Multi-Center Study in Asia

BackgroundMaintenance is a part of standard practice in multiple myeloma patients receiving induction followed by autologous stem cell transplantation (ASCT). Various regimens including thalidomide, lenalidomide and proteasome inhibitor are used as maintenance treatment. However, few prospective trials have been performed evaluating maintenance treatment in Asian myeloma patients. In this prospective multi-center trial, we evaluated the efficacy and toxicity of thalidomide-based maintenance therapy in Korean myeloma patients.MethodsWe conducted an open-label, prospective, multicenter phase II study. Patients with newly diagnosed multiple myeloma who underwent induction followed by ASCT were enrolled. Patients should not have refractoriness to previous thalidomide if the drug is included in induction regimen, and should have achieved at least partial response (PR) after ASCT. Patients received maintenance treatment of 100mg thalidomide daily for 28 days and 40mg dexamethasone for 4 days. The maintenance therapy was continued for one year unless there were disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was 1-year event-free-survival (EFS). Progression free survival (PFS), overall survival (OS), drug tolerability and safety were also evaluated.ResultsA total of 43 patients were enrolled. One-year EFS rate was 60.47% (95% confidence interval (CI), 44.34-73.26%). Progression-free survival (PFS) was 86.05% at 1-year and 72.09% at 2-year. Overall survival (OS) at 1-year and 2-year was 90.70% and 88.37%, respectively. Among 21 patients who did not acquire complete remission (CR) after ASCT, 4 patients reached CR after maintenance therapy. The maintenance treatment was discontinued in 15 patients (34.9%). The most common cause was adverse events (6 patients) followed by disease progression (4 patients). Rest of the patients terminated the treatment by patient's withdrawal (3 patients) and investigator's decision (2 patients). In each cycle, up to 23.3% of patients experienced dose reduction or delayed medication. Two leading causes of the schedule change were the adverse event and physician's decision. Grade 3 or 4 hematologic adverse events (AE) was upper respiratory infection (20 patients, 46.5%) followed by peripheral neuropathy (19 patients, 44.2%). Among the patients with neuropathy, 2 patients showed more than grade 3 symptom. Two patients showed serious adverse events (pneumonia and fulminant hepatitis). Thromboprophylaxis was performed in 37 patients using aspirin and one patient developed deep vein thrombosis during maintenance.ConclusionsThalidomide and dexamethasone maintenance for transplant eligible, newly diagnosed Korean multiple myeloma patients showed 1-year EFS and OS rate of 60.47% and 90.70% which is similar to the reports from western countries. Thalidomide and dexamethasone were tolerable as maintenance in Asian patients, although high hematologic toxicity draws concern. We concluded that thalidomide-based maintenance therapy is one of suitable option in Asian transplant eligible, newly diagnosed multiple myeloma patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Chemotherapy Relative Dose Intensity, Overall Survival, and Hematologic Toxicity in Solid-Tumor Cancer Patients: A Literature Review and Meta-Analysis

Background: Reduction in chemotherapy relative dose intensity (RDI) is a common outcome of hematologic toxicity during cancer chemotherapy and can affect treatment efficacy and, consequently, survival time. Several published studies have reported associations between RDI and overall survival, as well as the cumulative incidence of hematologic toxicities. A systematic literature review and meta-analysis of these results can elucidate opportunities to improve overall survival by managing hematologic toxicity. Methods: PubMed, Embase, and Web of Science databases were searched from 2013 through 2019 to identify studies reporting the associations of chemotherapy RDI with survival in adult solid-tumor cancer patients. Titles and abstracts of articles were reviewed and after excluding irrelevant studies, two independent reviewers assessed the de-duplicated, full-text articles and abstracted relevant studies into an extraction database. Endpoints included overall and progression-free survival by RDI and the cumulative incidence of grade 3 or higher hematologic adverse events. Eligible publications included observational studies and clinical trials published in English from peer-reviewed journals and conference abstracts. Random-effects meta-analyses were conducted to quantify the association between RDI levels and overall survival using studies reporting a hazard ratio (HR) for overall survival by tumor type, chemotherapy regimen, and RDI threshold of 80% or 85%. The results of included outcomes were summarized across available studies, weighting studies by the inverse of their variance. Study heterogeneity was evaluated using Cochran's Q and I2 statistical tests. Summary HR and 95% confidence intervals (CI) were represented using forest plots. Results: After reviewing 914 articles resulting from the literature searches, a total of 41 studies were included in the extraction database. Overall, two major categories of studies were identified: platinum-based regimens for breast, non-small cell lung cancer, or ovarian cancer; and 5-fluorouracil-based regimens (e.g. FOLFOX, FOLFIRI) for colorectal or pancreatic cancer. Meta-analysis of the five platinum-based studies (HR 1.17; 95% CI: 1.07-1.27) and four 5-fluorouracil-based studies (HR 1.39; 95% CI: 1.03-1.89) demonstrated significantly shorter survival time at RDI levels &amp;lt;80/85% vs. RDI levels ≥80/85% (Figure 1). Grade 3 or higher hematologic toxicities were reported by nine studies (two with age stratification). The cumulative incidence estimates of grade 3+ hematologic adverse events were higher for platinum-based regimens (14-22% for thrombocytopenia; 15-19% for anemia; and 24-58% for neutropenia) than 5-fluorouracil regimens (1-4% for thrombocytopenia; 5-19% for anemia; and 19-47% for neutropenia). In each study, neutropenia incidence was higher (0-58% across studies) than anemia (5-28%) and thrombocytopenia (1-22%) (Figure 2). Thrombocytopenia and anemia incidence were higher with paclitaxel in pancreas and ovarian cancers than other therapies. Hematologic toxicities were not reported separately by RDI in these studies. Conclusions: Recent publications demonstrated longer survival with RDI ≥80/85% than with lower RDI for solid tumor cancer patients on platinum-based and 5-fluorouracil-based chemotherapy regimens. Grade 3+ hematologic toxicities commonly occurred in studies of platinum-based regimens and some 5-fluorouracil studies. Managing such toxicities may contribute to maintenance of higher RDI and ultimately benefit overall survival. Disclosures Bylsma: EpidStrategies: Current Employment. Nielson:Amgen Inc: Current Employment. Fryzek:EpidStrategies: Current Employment. Saad:Amgen Inc: Current Employment.

Association between Sternal Dosimetric Parameters and Acute Hematological Toxicity of Radiotherapy after Modified Radical Mastectomy for Breast Cancer

To research the association between sternal dosimetric parameters and hematological toxicity of radiotherapy after modified radical mastectomy for breast cancer. We retrospectively analyzed the complete clinical data and radiotherapy data of 58 patients treated with radiotherapy after modified radical mastectomy. V5、V10、V20、V30、V40、Dmean、Dmax、D20、D40、D60、D80 of the sternum were recorded on dose-volume histogram. Collecting and sorting of patients with clinical parameters: such as ages, height, body weight, etc.14 indexes. The hematological indexes were recorded before and during radiotherapy; Hematological toxicity was graded according to (NCI-CTC)4.0. Simple linear correlation was used to test the relationship between clinical parameters, dosimetric parameters and blood cells nadir, and Logistic regression model was used to test the correlation between dosimetric parameters and the incidence of blood cell toxicity. The Receiver Operating Characteristic (ROC) curve is used to evaluate the cutoff values of dosimetric parameters to avoid hematological toxicity. Univariate factor Logistic analysis: sternum V20、V30、V40 were associated with increased risk ≥2 grade hematological toxicity; sternum V10、V20、V30、V40、D60、D80 was associated with increased risk≥2 grade leukopenia; Sternum V5 and V10 were associated with≥3 lymphocytopenia(P<0.1). Multivariate factor Logistic analysis: Sternum V30 is an independent risk factor for≥2 grade acute hematological toxicity (P = 0.031); Sternum V40 and D80 were independent risk factors for toxicity≥2 grade leukopenia (P = 0.009, P = 0.05). The cut-off point of V30 、V40、D80 was 24.38cm3、 6.48cm3、23.37Gy respectively. When sternal V30 ≥24.38cm3, the incidence of ≥grade 2 HT increased significantly (89%、37% P<0.001); when sternal V40 ≥ 6.48cm3, the incidence of ≥ 2 grade leukopenia increased significantly (64%、24% P = 0.003).When sternum D80 ≥23.37Gy, the incidence of ≥2 grade leukopenia increased significantly(75%、36% P = 0.008).In addition, clinical parameters related to hematological toxicity were also found. White blood cell and lymphocyte Count at baseline were associated with≥2 grade leukopenia and≥3 grade lymphocytopenia, respectively (P = 0.009、P = 0.005). Higher ki-67 and higher chemotherapy-radiotherapy time interval were more likely to cause grade≥2 neutropenia (P = 0.016、P = 0.025). Further studies on factors influencing sternal dose showed that Thoracic ratio and BMI were negatively correlated with sternal V40 (β = -0.304 P = 0.02、β = -0.259 P = 0.05). For patients receiving adjuvant radiotherapy after modified radical mastectomy for breast cancer, reducing the sternal dose can reduce the incidence of grade 2 or higher hematological toxicity. In addition, some clinical parameters such as baseline values of blood cells, ki-67, and time interval of chemoradiotherapy can also affect hematological toxicity, which should be paid enough attention.

Impact Of Adding Induction Chemotherapy To Chemoradiotherapy In The Management Of Locally Advanced Squamous Cell Cancers Of The Head And Neck Presenting With Radiographic Extranodal Extension

In patients with locally advanced squamous cell cancers of the head and neck (LAHNC), the presence of radiographic extranodal extension (rENE) is known to predict for worse local control (LC), distant control (DC), and overall survival (OS). We investigated whether the addition of induction chemotherapy (IC-CRT) to standard chemoradiation (CRT) improved outcomes among this population. From our IRB approved database, we conducted a single-institution retrospective study of patients with LAHNC who were determined to have rENE by an expert head and neck radiologist and underwent definitive therapy with either IC-CRT or CRT. Kaplan-Meier analyses were performed to evaluate impact of treatment regimen (IC-CRT vs CRT) on locoregional control (LRC), distant control (DC), and OS. Survival was calculated from time of pathologic diagnosis. Cox regression multivariate analyses evaluated for independent predictors of survival. Toxicity was evaluated using CTCAE v4.0 and acute toxicity was defined as occurring within 3 months of starting treatment. The association between IC and acute toxicity was evaluated using Chi-Square analysis. Of 141 LAHNC patients who were identified with rENE, 68 received IC-CRT and 73 received CRT. Radiation dose was generally 70Gy and 68% of IC was TPF regimen, of whom 98% completed 2-3 cycles. Median follow up was 4.8 years, and among survivors was 7.1 years. At time of analysis, 52 patients (37%) had died. AJCC 8th edition stage was not significantly different between treatment groups (p = 0.14). Comparing IC-CRT vs. CRT, patients achieved similar 5-year LRC (79.8% vs 68.5%, p = 0.33), DC (73.1% vs 71.9%, p = 0.64), and OS (64.6% vs 59.0%, p = 0.62). Among patients with p16 negative disease (n = 52; 29 IC-CRT vs. 23 CRT, similar stages p = 0.27), use of IC-CRT vs. CRT yielded improved 5-year LRC (78.3% vs 38.4%, p = 0.02), while DC (65.1% vs 63.6%, p = 0.15) and OS (54.8% vs 38.3%, p = 0.23) was similar. MVA showed a trend toward improved LRC for p16 negative cancer with use of IC-CRT (HR 0.33, 95% CI: 0.14-1.10, p = 0.07). Acute grade 3-5 toxicity was significantly more prevalent with IC-CRT than CRT (71% vs 51%, p = 0.01), driven by higher hematologic toxicity (56% vs 33%, p = 0.006). In these long-term results of a retrospective series of patients with LAHNC and rENE, patients who received IC-CRT demonstrated similar LRC, DC, and OS vs. standard CRT. For patients with p16-negative disease, IC-CRT yielded significantly improved LRC. Nevertheless, IC-CRT was associated with worse toxicity, and additional studies are needed to examine ideal treatment strategies among this poorly performing population.

Pelvic bone marrow sparing intensity modulated radiotherapy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving concurrent chemoradiotherapy: a single-center prospective randomized controlled trial

PurposeTo test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiotherapy (PBMS-IMRT) in reducing grade 2 or higher hematological toxicity (HT2+) for patients with cervical cancer treated with concurrent chemoradiotherapy.Methods and materialsA total of 164 patients with Stage Ib2–IIIb cervical cancer were prospectively enrolled from March 2018 to March 2019 at a single center and were randomly allocated into the PBMS group or the control group. The control group received weekly cisplatin concurrently with IMRT, followed by intracavitary brachytherapy. The PBMS group additionally received PBM dose constraint. The dosimetric parameters of the pelvic bone (PB) and the subsites including hip bone (HIP) and lumbosacral spine (LSS) and the corresponding bone marrow were recorded. The endpoint of the trial was acute hematologic or gastrointestinal toxicity. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints.ResultsEighty-two patients in the PBMS group and 82 in the control group were enrolled for statistical analysis. The incidence of HT2+ in the PBMS group was 50.0%, significantly lower than the 69.5% incidence in the control group (P = 0.02). Patients with PB V40 ≥ 28% were more likely to experience HT2+ (OR = 2.85, P = 0.006), while the incidence of grade 2 or higher gastrointestinal toxicity (GT2+) events did not differ significantly between the two groups (P > 0.05). Dosimetric parameters of LSS showed stronger associations with HT2+ than other subsites. The patients with LSS V10 ≥ 87% and LSS mean ≥ 39 Gy were more likely to experience HT2+ (OR = 3.13, P = 0.001;OR = 3.03, P = 0.002, respectively).ConclusionPBMS-IMRT reduced HT compared with IMRT alone. Efforts to maintain LSS V10 < 87%, LSS mean < 39 Gy and PB V40 < 28% simultaneously may reduce the risk of HT2 +.Trial registrationThe trial was registered with Chinese clinical trial registry (ChiCTR1800015069).

Impact of radiotherapy on risk of adverse events in patients receiving immunotherapy: A U.S. Food and Drug Administration pooled analysis.

3018 Background: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of multiple advanced malignancies. Radiotherapy (RT) has been used in combination with ICIs to activate tumor-specific T cell responses, and RT also promotes non-specific acute and chronic inflammatory responses both locally and systemically. More than 50% of patients receive RT at some point during their course of cancer therapy, and relatively little information is available pertaining to the impact of RT, if any, on the risk of adverse events (AEs) in patients receiving ICIs. Methods: Pooled data from prospective trials of ICIs submitted to the FDA in initial or supplemental BLAs or NDAs through 12/2019 were included (N=66). Trials from applications that were withdrawn or not approved were not included. Patients were subdivided by whether or not radiotherapy was administered at any time during the course of their cancer treatment. AEs common to both ICI treatment and RT were identified to focus on the following reactions: neutropenia, thrombocytopenia, colitis, hepatitis, pneumonitis, and myocarditis. Descriptive statistics were used to examine AEs associated with the use of radiation and ICIs. Results: A total of 25,836 patients were identified, of which 9087 (35%) received RT and 16,749 (65%) did not. Radiation was associated with similar rates of AEs overall with numerically higher hematologic toxicities and pneumonitis and numerically lower colitis, hepatitis and myocarditis (Table). Patients receiving RT were more likely to experience Grade 3-5 hematologic toxicities compared to those not receiving RT. Conclusions: To our knowledge, this is the largest report of AE risk associated with the use of radiation and ICIs. Our results show that the incidence of hematologic toxicity and pneumonitis in patients receiving RT may be slightly higher. Analysis to determine comparability of baseline demographic characteristics, comprehensive AE profile, and timing of RT is underway. [Table: see text]

Efficacy of cisplatin combined with topotecan in patients with advanced or recurrent ovarian cancer as second- or higher-line palliative chemotherapy.

The aim of this study was to evaluate the outcomes of patients with advanced or recurrent ovarian cancer treated with cisplatin combined with topotecan as second- or higher-line palliative chemotherapy.We retrospectively reviewed the medical records of patients with advanced or recurrent ovarian cancer, who were treated with cisplatin (50 mg/m on day 1) and topotecan (0.75 mg/m on days 1-3). Treatment response, progression-free survival (PFS) and overall survival (OS) were analyzed, and laboratory data were reviewed to evaluate toxicities.Thirty one patients were treated with cisplatin and topotecan. The objective response rate (ORR) was 22.6%, and the disease control rate (DCR) was 61.3%. The median PFS was 3.7 months (95% confidence interval [CI], 2.3-5.2 months) and the median OS was 44.5 months (95% CI, 35.5-53.5 months). The ORR (33.3% vs. 0%; P = .012) was significantly better in the platinum-sensitive group compared to the platinum-resistant group. The median PFS was significantly longer in the platinum-sensitive group compared to the platinum-resistant group (7.7 vs 2.5 months; P < .001), and the median OS was also significantly longer in the platinum-sensitive group (46.6 vs 19.3 months; P < .001). Almost all of the patients reported some degree of hematological toxicity. A high rate of grade 3-4 neutropenia (87.1%) was observed. Grade 3-4 thrombocytopenia (41.9%) and febrile neutropenia (19.4%) were also seen.The results showed that cisplatin combined with topotecan, as second- or higher-line palliative chemotherapy for patients with advanced or recurrent ovarian cancer, might be effective, especially in the platinum-sensitive group. However, attention should be paid to the high hematological toxicity associated with this drug combination.