Chemotherapy Dose Reductions Research Articles

Usefulness of Prophylactic Administration of Pegfilgrastim for Esophageal Cancer Chemotherapy: A Single-center Retrospective Study.

To evaluate the impact of prophylactic administration of pegfilgrastim in esophageal cancer (EC) patients treated with chemotherapy consisted of docetaxel, cisplatin, and fluorouracil (DCF). Among 102 patients who received neoadjuvant or induction DCF for primary advanced EC, 65 received prophylactic pegfilgrastim and 37 did not. The association of pegfilgrastim with adverse events and clinicopathological outcomes was retrospectively analyzed. In the pegfilgrastim group, the incidence of grade >3 neutropenia was lower (30.8% vs. 62.2%) and more patients avoided dose reduction or discontinuation of chemotherapy (32.3% vs. 70.3%). The radiological (PR≤) and histopathological (grade 1b≤) response rates were significantly higher (69.2% vs. 43.2% and 59.2% vs. 35.7%). Three-year overall survival and progression-free survival rates were significantly higher (65.0% vs. 48.6%, p=0.033; 56.1% vs. 35.1%, p=0.007, respectively). Prophylactic pegfilgrastim in DCF may relieve adverse events and improve the oncologic outcome of EC patients.

Prevalence and Associated Factors of Anemia among Breast Cancer Patients Undergoing Chemotherapy: A Prospective Study.

Purpose The purpose of this study was to ascertain the prevalence and factors associated with anemia (hemoglobin [Hb] 12 g/dL) in breast cancer patients undergoing chemotherapy. Materials and Methods We conducted a prospective longitudinal study to collect demographic and clinical data on adult breast cancer patients with or without anemia who were admitted to HKL, UMMC, and NCI. The incidence of anemia was determined by detecting whether or not anemia developed during the course of chemotherapy. Mild, moderate, or severe anemia was defined. A chi-squared and logistic regression model were used to assess the effect of demographic and clinical factors on the incidence of anemia and multiple logistic regression analysis was used to evaluate the associations of potential risk factors with the presence of CRA. Results The study enrolled a total of 292 breast cancer patients. Anemia occurred at a rate of 41.1% (n = 120). Our findings indicated that clinical factors such as the number of chemotherapy regimens, dose reduction, and type of chemotherapy, for example, docetaxel, as well as demographic covariates such as age and BMI, all contribute to the incidence of anemia in cancer patients. Conclusions According to this study, the prevalence of anemia in breast cancer patients is high. Patients' age, BMI, number of chemotherapy regimens, and docetaxel were risk factors; thus, protocols are needed to identify subgroups of breast cancer likely to benefit from novel management strategies.

Therapeutic plasma exchange for multiorgan dysfunction among critically ill pediatric patients with leukemia: A single-institutional experience.

Therapeutic plasma exchange (TPE) has well-documented applications in the adult population, outlined by the American Society for Apheresis (ASFA) 2019 guidelines. Limited data exist regarding the use of TPE in critically ill pediatric patients; however, these reports rarely include patients with oncological diseases. We highlight the use of TPE in the acute management of seven pediatric patients with leukemia treated at Children's Mercy Hospital ICU from 2015 to 2020, including TPE specifications, baseline and interval laboratory evaluation, and outcome measures. Analysis compared those who did (n=4) and did not (n=3) survive 30 days post-TPE. Multiorgan failure (MOF) prompted the initiation of TPE in 85.7% of patients, 57.1% of whom were also diagnosed with hemophagocytic lymphohistiocytosis (HLH). Baseline laboratory evaluations prior to initiation of TPE were similar between the two groups. With subsequent TPE treatments, C-reactive protein (CRP) and lactic acid decreased. CRP and lactic acid following the last TPE treatment were significantly higher for those deceased 30 days post-TPE (P = .023 and .031, respectively). No TPE-associated adverse events necessitated discontinuation of TPE treatment. Several surviving patients required chemotherapy dose reductions or alterations. Our cohort demonstrated MOF and HLH consistently as indications for TPE, currently ASFA category III indications (optimal role of apheresis is not yet established). Recognition of this treatment modality earlier in the clinical course for critically ill oncological patients may lead to the development of formal protocols that may result in earlier initiation of TPE and improved outcomes.

SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea and vomiting (2021)

Among the side effects of anticancer treatment, chemotherapy-induced nausea and vomiting (CINV) is one of the most feared given its high prevalence, affecting up to 40% of patients. It can impair patient’s quality of life and provoke low adherence to cancer treatment or chemotherapy dose reductions that can comprise treatment efficacy. Suffering CINV depends on factors related to the intrinsic emetogenicity of antineoplastic drugs and on patient characteristics. CINV can appear at different times regarding the administration of antitumor treatment and the variability of risk according to the different antitumor regimens has, as a consequence, the need for a different and adapted antiemetic treatment prophylaxis to achieve the desired objective of complete protection of the patient in the acute phase, in the late phase and in the global phase of emesis. As a basis for the recommendations, the level of emetogenicity of anticancer treatment is considered and they are classified as high, moderate, low and minimal emetogenicity and these recommendations are based on the use of antiemetic drugs with a high therapeutic index: anti 5-HT, anti-NK and steroids. Despite having highly effective treatments, clinical reality shows that they are not applied enough, so evidence-based recommendations are needed to show the best options and help in decision-making. To cover all the antiemetic prophylaxis options, we have also included recommendations for oral treatments, multiday regimens and radiation-induced emesis prevention.

Exploring Clinicians' Perspectives of Barriers to Chemotherapy-Induced Peripheral Neuropathy Assessment and Management in Oncology Practice: A Qualitative Analysis of Semi-structured Interviews.

Quantitative reports suggest that the assessment and management of chemotherapy-induced peripheral neuropathy (CIPN) in practice is suboptimal. The purpose of this qualitative analysis was to explore clinician-related perspectives of CIPN assessment, management, and the use of a CIPN decision support tool. Clinicians from the breast oncology, gastrointestinal oncology, or multiple myeloma disease centers at Dana-Farber Cancer Institute who interacted with a CIPN clinician decision support algorithm were eligible to participate in the semi-structured interviews. The interview guide included questions about CIPN assessment, management, and clinician-decision support tool use. All interviews were audio-recorded, transcribed, and analyzed using inductive content analysis. Of the 39 eligible clinicians, 15 agreed to be interviewed. Interviewed clinicians were mainly physicians (73.3) and White, non-Hispanic (93.3%). Main themes from the interviews included (1) CIPN management practice patterns (eg, endorsement of non-recommended management strategies or lack of standardization for chemotherapy dose reduction) and barriers (eg, insurance prior authorizations required for duloxetine prescription), (2) CIPN assessment practice patterns (eg, use of subjective instead of objective CIPN assessment approaches) and barriers (eg, difficult to interpret patients' CIPN report between visits), and (3) utilization of the clinician decision support tool (eg, all assessment tasks lead to same management options). There are several barriers to clinicians' use of evidence-based CIPN assessment and management strategies. Future work should be focused on addressing barriers to duloxetine prescription, developing evidence-based CIPN assessment and management strategies, improving symptom monitoring, and facilitating referrals to existing supportive care services.

Romiplostim for chemotherapy‐induced thrombocytopenia: Efficacy and safety of extended use

BackgroundChemotherapy‐induced thrombocytopenia (CIT) is common during treatment with antineoplastic therapies and may adversely impact chemotherapy dose intensity. There is no approved therapy for CIT. In our recent phase II randomized study, romiplostim led to correction of platelet counts in 85% of treated patients and allowed resumption of chemotherapy, with low rates of recurrent CIT in the first two cycles or 8 weeks of chemotherapy. However, there is a lack of long‐term data on the efficacy and safety of romiplostim in CIT. ObjectivesTo analyze efficacy and safety of romiplostim in the patients in the phase 2 study, who received romiplostim for ≥1 year. Patients/MethodsTwenty‐one patients remained on romiplostim for ≥1 year. We analyzed the effect of romiplostim on platelet counts, absolute neutrophil counts, and hemoglobin, as well as impact on ongoing chemotherapy. We also tracked venous or arterial thrombotic events. ResultsDuring the study period, romiplostim was effective in preventing reduction of chemotherapy dose intensity due to CIT. Fourteen of the 20 (70%) analyzable patients experienced no episode of CIT, 4 subjects experienced a single chemotherapy dose delay due CIT, and 2 patients required a chemotherapy dose reduction. Platelet counts were preserved throughout the duration of the extension analysis. One patient experienced a proximal deep vein thrombosis, and one patient experienced multiple tumor‐related ischemic events. ConclusionsLong‐term use of romiplostim for treatment of CIT was effective and safe, with no evidence of resistance or increased risk of thrombosis.

Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial

Chemotherapy-induced thrombocytopenia is common and causes chemotherapy dose reductions or treatment delays, bleeding, and suboptimal oncological outcomes. We aimed to evaluate avatrombopag, a thrombopoietin receptor agonist that increases platelet counts, in patients with non-haematological cancer and platelet counts lower than 50 ×109 cells per L. In this randomised, double-blind, placebo-controlled, phase 3 study, patients aged 18 years or older at 71 hospitals or cancer treatment centres in China, Hungary, Poland, Russia, Serbia, Ukraine, and the USA and with ovarian, bladder, or lung cancer receiving chemotherapy who had severe thrombocytopenia were randomly assigned (2:1) to oral avatrombopag 60 mg or oral placebo once daily given 5 days before and after chemotherapy, with randomisation stratified by number of chemotherapy drugs used. Patients, investigators, and data collectors were masked to group allocation. Eligibility required two previous lines of chemotherapy or fewer, an ECOG performance status of 2 or less, and no previous history of chemotherapy-induced thrombocytopenia. The composite primary endpoint was the proportion of responders not requiring platelet transfusion or either a 15% or more chemotherapy dose reduction or a 4-day or more chemotherapy delay due to thrombocytopenia following study treatment until the start of the subsequent cycle. Analyses were done on the intention-to-treat and per protocol populations. Safety was analysed in all patients who received at least one dose of avatrombopag. The trial is registered with ClinicalTrials.gov, NCT03471078, and has been completed. Between Oct 12, 2018, and June 28, 2020, 122 patients were enrolled and randomly assigned to receive avatrombopag (n=82) or placebo (n=40). Median follow-up was 31 days (IQR 22-61). Similar proportions of patients reached the primary endpoint in the avatrombopag and placebo groups (intention-to-treat: 57 [70%, 95% CI 58-79] of 82 vs 29 [73%, 95% CI 56-85] of 40; difference -3·0% (95% CI -21·6 to 15·6); p=0·72; per protocol: 51 [85%, 95% CI 73-93] of 60 vs 27 [84%, 95% CI 67-95] of 32; 0·6% (95% CI -20·8 to 22·1); p=0·96). 15 (18%) of 82 patients had serious adverse events in the avatrombopag group and eight (20%) of 40 in the placebo group, of which thrombocytopenia was most common (4 [5%] of 82 and 4 [10%] of 40 patients). Common grade 3-4 treatment-emergent adverse events were neutropenia (22 [27%] of 82 and 16 [40%] of 40 patients), leukopenia (19 [23%] of 82 and 5 [13%] of 40), anaemia (16 [20%] of 82 and 9 [23%] of 40), and thrombocytopenia (16 [20%] of 82 and 14 [35%] of 40). Most adverse events were considered unrelated to study drug. No treatment-related deaths were reported. In this population of patients with non-haematological malignancies who are relatively chemotherapy naive, chemotherapy-induced thrombocytopenia treatment outcomes were similar between the avatrombopag and placebo groups. Given its safety and ability to augment platelet counts in patients with chemotherapy-induced thrombocytopenia, evaluation of avatrombopag in populations with more persistent chemotherapy-induced thrombocytopenia is warranted. Dova Pharmaceuticals, a Sobi company.

Abstract OT2-21-01: A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G)

Abstract Background: Current guidelines recommend the use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis to prevent febrile neutropenia (FN) associated with commonly used breast cancer chemotherapy regimens. Filgrastim (FIL) is a short-acting G-CSF injection that requires daily subcutaneous injection starting 24-72 hours after chemotherapy for 5 to 10 days. Pegfilgrastim (PEG) is a long-acting, pegylated formulation that requires a single injection 24-72 hours after chemotherapy. G-CSF causes bone pain in approximately 70% of patients, which can be severe in over 25% of cases. While registration trials for PEG showed bone pain from PEG was comparable to FIL when given for a median duration of 11 days, many oncologists are now only prescribing FIL for 5 days based on a multicenter RCT showing that 5 days of FIL is non-inferior to 7 or 10 days of FIL in terms of FN and treatment-related hospitalizations. Furthermore, the cost of 5 days of FIL ($CA 721.55 for 300 mcg dose) is half of the price of a single dose of PEG ($CA 1424.63). Therefore, if 5 days of FIL leads to significantly less bone pain, this may improve health-related quality of life (HR-QoL) for patients, improve adherence to G-CSF, and improve cost-effectiveness. Methods: Patients receiving neo-/adjuvant chemotherapy for early stage breast cancer requiring primary FN prophylaxis with G-CSF will be approached for this pragmatic, multicenter, open-label superiority RCT. Using the Rethinking Clinical Trials (REaCT) methodology that incorporates an integrated oral consent model, eligible and consented patients will be randomized to either 5 days of FIL or one day of PEG with each cycle of chemotherapy. The primary endpoint is bone pain during the first 5 days after G-CSF injection using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) of the Bone Pain Diary. Secondary endpoints include incidence of FN and treatment-related hospitalizations, incidence of chemotherapy delay, dose-reduction, or discontinuation, incidence of chemotherapy-related mortality, rate of G-CSF compliance, healthcare resource utilization, HR-QoL, and cost-effectiveness. Participants will also complete a Treatment Preference Questionnaire (TPQ) exploring the relative importance of different factors in deciding between PEG vs. 5 days of FIL both before randomization and at the end of the study. To achieve 80% power in an ANCOVA analysis and assuming 5% are loss to follow-up, the planned sample size is 232 patients (116 per arm). The randomization (1:1 ratio) will be stratified by treatment center (4 centers) and chemotherapy regimen (taxane-based vs. anthracycline-based in the first 4 cycles). Results: The study opened for enrollment on June 9, 2021. As of July 6, 2021, the study has opened at one site, and 13 patients have been randomized.Conclusion: This will be the first RCT using a patient-reported Bone Pain Diary that was co-developed by patient partners to measure bone pain between 5 days of FIL vs. PEG. In collaboration with patient partners, the study incorporates a tool (TPQ) that explores factors that may be important in deciding between PEG and FIL, with the aim of translating the findings of this study into real world clinical practice. Citation Format: Terry L. Ng, Monica Taljaard, Marie-France Savard, Carol Stober, Stuart Nicholls, Lisa Vandermeer, Kednapa Thavorn, Claudia Hampel, Jennifer Shamess, Natalie Mills, John F. Hilton, Mark Clemons. A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-21-01.

Comprehensive evaluation of risk factors for the development and complications of chemotherapy-induced febrile neutropenia

Febrile neutropenia is a serious adverse effect of chemotherapy. It can lead to complications and death, as well as delays in treatment, chemotherapy dose reductions, compromised treatment efficacy, and reduced survival. The assessment of the patient-related risk factors plays a significant role in the prevention of febrile neutropenia and its complications. In the case of intermediate-risk chemotherapy, the patient-related factors contribute to the estimation of an overall febrile neutropenia risk as well as to timely planning of primary prophylaxis using growth factors. Patients presenting with febrile neutropenia undergo a detailed initial risk assessment for serious complications so that an appropriate treatment can be selected. Recommendations given by the guidelines outline the classification of and risk factors for febrile neutropenia complications. The use of patient-related factors and validated tools for the risk assessment of complications makes it possible to optimize the treatment for each patient and to reduce the risk of morbidity and mortality due to febrile neutropenia.

Romiplostim – A narrative drug review

Chemotherapy-induced thrombocytopenia (CIT) is a challenging condition that is routinely encountered in oncology practice. Currently, the sole therapeutic modality for CIT is the transfusion of platelets, especially when the platelet count is less than 20,000 per microliter. Chemotherapy dose reductions and dose delays result, which may lead to compromised outcomes. Drugs like oprelvekin and avatrombopag have been tried for CIT, but are not in routine use due to severe adverse effects. Romiplostim and eltrombopag are thrombopoietin receptor agonists that have been successfully used in benign conditions like idiopathic thrombocytopenic purpura (ITP), but are not approved for use in CIT. We searched PubMed for studies published in the last 5 years (2017–2021), using the key words “romiplostim,” “cancer,” and “malignancy”. We excluded articles that were related to benign causes of thrombocytopenia, articles for which the full text was not available, non-human studies, and articles in a language other than English. A total of 34 articles were included. In this narrative drug review, we have focused on romiplostim and the evidence supporting its use in both solid and hematologic malignancies.

A sequential exploratory study to develop and validate neutropenic nursing care bundle for neutropenic patients admitted in a tertiary care hospital, Uttarakhand.

Patients diagnosed with cancer and who undergo cancer treatment are at potential risk of bone marrow suppression leading to prolonged hospitalization, delay in treatment, and chemotherapy dose reductions, which ultimately results in significant morbidity and mortality. This sequential exploratory study using a mixed-method approach was aimed to develop and validate a neutropenic nursing care (NNC) bundle for neutropenic patients admitted in a tertiary care hospital, Uttarakhand. This sequential exploratory study design with an instrument developmental model was used to develop the NNC bundle. It consisted of two phases: Qualitative phase and quantitative phase. In the qualitative phase, focused group discussion with eight oncology nurses was performed to derive themes related to neutropenic nursing care using conventional content analysis. An extensive literature review was also performed on these themes to explore the current pieces of evidence for item pool generation. In the quantitative phase, a preliminary draft bundle was developed, and two Delphi rounds (I and II) were carried out among the five experts for the content validation of the NNC bundle and a final bundle was developed. Major domains identified for the bundle were hand hygiene, care of central and peripheral lines, routine oral care, antiseptic bath, peri-anal care, diet, and environmental hygiene. The content validity index (CVI) of the bundle was found to be >80% for all the items with I-CVI >0.8 and S-CVI = 0.99 after conducting two rounds of Delphi. The present study has provided a set of valid written neutropenic nursing interventions to prevent complications in neutropenic patients. The NNC bundle should be subjected to other levels of evaluation that measure the bundle's practicability and suitability for the intended field.

Survival Outcomes With Reduced Doses of Adjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer.

There have not been enough recent studies investigating the incidence or efficacy of dose reduction in adjuvant chemotherapy for epithelial ovarian cancer. This study examined whether patients who needed dose reduction showed poorer survival outcomes. From 2011 to 2021, 102 patients were included in the study. Patients who underwent neoadjuvant chemotherapy and those with early-stage disease were excluded. Patients were divided into two groups: those who had a ≥60% dose reduction during the whole period of first-line adjuvant chemotherapy, and those with dose reductions <60%. Of the 102 patients, 38 (37.3%) underwent dose reduction ≥60%. PFS was significantly longer in the group whose dose reductions were ≥60%, whereas OS was not significant. A dose reduction of ≥60%, determined by patients' medical conditions, during first-line of adjuvant chemotherapy does not negatively influence survival outcomes, such as OS and PFS, in advanced epithelial ovarian cancer.

Real-World Outcome of Platinum-Based Chemotherapy in Advanced Breast Cancer (ABC): A Retrospective Study from a Tertiary Cancer Center in India

Abstract Introduction There is a paucity of data on platinum-based chemotherapy in advanced breast cancer (ABC) from developing countries like India. Objectives The objectives were to analyze the efficacy and safety of platinum-based chemotherapy in patients with ABC. Materials and Methods This was a retrospective study of 35 patients with ABC who were treated with platinum-based chemotherapy (gemcitabine and carboplatin, [GC]) in a tertiary cancer center in India from August 2015 to November 2019. The inclusion criteria were patients with ABC, who had received palliative chemotherapy with GC. The exclusion criteria were patients who had received less than two cycles of GC and patients who received platinum-based chemotherapy for neuroendocrine carcinoma of the breast. Results The median age was 45 years (range: 28–68 years). All patients were female (97%) except one male (3%). The histology was ductal carcinoma (77%), mixed (17%), and others (6%). Out of the 12 patients tested for breast cancer (BRCA) gene mutation, six patients had a BRCA mutation. Patients with metastatic and locally progressive disease were 91 and 9%, respectively. The median number of prior lines of systemic therapy for metastatic disease was 1 (range: 0–5). The median number of sites of metastasis was 2 (range: 0–5). Patients with visceral crises were 23%. The median number of cycles of GC chemotherapy received was 6 (range: 2–6). A dose reduction in chemotherapy was done in 74%. The responses among 34 evaluable patients were complete response (11%), partial response (24%), stable disease (41%), and progressive disease (24%). Grade 3 or more hematological and nonhematological toxicities were observed in 69 and 9%, respectively. The median progression-free survival and overall survival were 6 and 8 months, respectively. The 1-year progression-free survival and overall survival were 19 and 34%, respectively. Multivariate analysis showed that patients who had received more than 3 cycles had a better outcome. Conclusion GC was an active and well-tolerated regimen in ABC regardless of the receptor status. Further prospective randomized studies are warranted to assess the optimal regimen in patients with triple-negative breast cancer.

Effects of Complementary and Alternative Medicine on Chemotherapy Delivery in Thai Patients.

Background:Complementary and Alternative Medicine (CAM) is widely used among cancer patients worldwide. This prospective observational study aimed to show the effect of CAM use on chemotherapy delivery in Thai patients. Methods: During March 2014 to February 2015, the patients with breast, lung or colorectal cancer receiving first cycle chemotherapy at King Chulalongkorn Memorial Hospital were enrolled. The correlation between CAM using and chemotherapy schedule delay and dose reduction, dose intensity, quality of life and adverse event rates were analyzed. Results:There were 80 (44.20%) patients using CAM among 181 enrolled patients. Seventy six CAM users and 97 non-CAM users receiving 2nd cycle of chemotherapy were included for primary analysis. The chemotherapy schedules were delayed and/or reduced in 40 (52.6%) and 48 (49.5%) in CAM users and non-CAM users, respectively, p =0.681. The mean relative dose intensity (RDI) were 92.4% and 94.1% in CAM and non-CAM users, respectively, p=0.244. However, there were significantly more CAM users receiving chemotherapy less than 90% RDI (34.8% vs 19.8%, p=0.033). As compared to first cycle, at third cycle, the mean QOL score changes were -4.63 (95% CI -2.49-9.27) and -8.02 (-2.36- 9.142) in CAM user and non-CAM user, respectively (p=0.255). There were significantly higher rates of grade 3 or 4 anemia (5.1% vs 0%, p=0.024), and grade 2 malaise (19.0% vs 5.1%, p=0.004) in CAM users. Conclusions:There were similar overall rates of chemotherapy schedule delay and dose reduction between CAM- and non-CAM users. However, there were less CAM-users achieving 90% chemotherapy RDI.

First Line and Second Line Chemotherapy in Advanced Cholangiocarcinoma and Impact of Dose Reduction of Chemotherapy: A Retrospective Analysis.

ObjectivePrognosis of patients with irresectable cholangiocarcinoma is still poor. The ABC-02 trial established the current first line (1L) standard systemic chemotherapy (CT) with gemcitabine/platinum derivate for advanced cholangiocarcinoma. However, the majority of patients needed therapy adaptions. Thus, the aim of this study was to evaluate 1L and second line (2L) therapy regimens and the impact of therapy adaptions in an unselected real-life cohort of patients with advanced cholangiocarcinoma.Materials and MethodsThis is a single institution retrospective analysis of patients with irresectable cholangiocarcinoma who were treated with gemcitabine/platinum derivate from 2010 to 2018. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially with regard to CT de-escalation.ResultsFifty-eight patients receiving gemcitabine/platinum derivate were included in the analysis. Median OS and PFS were 12.2 and 6.9 months. Interestingly, 41 patients (71%) needed therapy de-escalation. However, despite reduced CT exposition, there was no-significant difference in OS (10.8 months vs. 15.6 months, p = 0.127), and patients suffered from less adverse events during CT. 21 (36%) patients reached 2L CT, most often with FOLFIRI (57%). Survival beyond the end of 1L CT was 7.1 months with 2L CT vs. 2.9 months with BSC.ConclusionIn our study, the combination of gemcitabine/platinum derivate showed similar OS and PFS as randomized prospective phase II/III trials. Therapy regimen adaptions were needed in the majority of patients. However, individualized modifications of the therapy regimen allowed better tolerance as well as continuation of therapy and did not significantly influence median OS. Furthermore, our study revealed a potential survival benefit with 2L CT for selected patients.

Meta-Analysis of Chemotherapy-Induced (Febrile) Neutropenia and Chemotherapy Disruptions Associated with Same-Day Versus Standard (24-72h) Pegfilgrastim Administration in Non-Hodgkin Lymphoma Patients

Background: While the product label and international guidelines recommend pegfilgrastim administration 24-72 hours following completion of chemotherapy, increasingly clinicians administer pegfilgrastim using a same-day protocol. We performed a meta-analysis to compare the incidence of febrile neutropenia (FN), chemotherapy-induced neutropenia (CIN) grade 4, and CIN/FN-related chemotherapy delays and dose reductions in non-Hodgkin lymphoma (NHL) patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone with or without rituximab (R±CHOP) who were provided with pegfilgrastim on the same-day of chemotherapy versus the standard 24-72h post-chemotherapy time window.Methods: Six databases were searched for studies that compared same-day pegfilgrastim with the standard regimen in NHL patients. Given the low heterogeneity (I 2<50%, Cochrane Q test P>0.10, fixed-effect model was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for all outcomes of interest.Results: We identified 7 studies, including one clinical trial (Burris et al. 2010) and six retrospective cohort studies (Woods et al. 2010, Ibrahim et al. 2011, Karol et al. 2013, Cheng et al. 2014, Bartels et al. 2021, McBride et al. 2021), that evaluated same-day versus standard 24-72h administration of pegfilgrastim in NHL patients. Results were statistically non-significant for all outcomes (Figure 1): FN across all chemotherapy cycles (OR=1.48, 95%CI= 0.98-2.23, P=0.06, N of studies=7); FN after the first cycle (OR=1.98, 95% CI=0.80-4.90, P=0.14, N=4); CIN grade 4 across all cycles (OR=0.73, 95% CI=0.37-1.47, P= 0.38, N=3); CIN grade 4 after the first cycle (OR=2.58, 95%CI= 0.86-7.73, P=0.09, N=3); and chemotherapy dose delays or reductions (OR=2.25, 95%CI=0.42-11.97, P= 0.34, N=2).Conclusion: In this independent study, the likelihood of developing FN and CIN grade 4 in the first cycle or across all chemotherapy cycles, and the likelihood of chemotherapy dose delays or reductions were statistically not different in NHL patients treated with R±CHOP and administered pegfilgrastim same-day or 24-72h post-chemotherapy. In the setting of NHL treated with R±CHOP, administering pegfilgrastim on the day of completion of chemotherapy may be a safe and effective method of prophylaxis. [Display omitted] DisclosuresAlrawashdh: Genentech: Current Employment. McBride: BMS: Current Employment. Abraham: Matrix45, LLC: Current holder of individual stocks in a privately-held company.

Efficacy and Safety of Extended Use of Romiplostim Treatment for Chemotherapy-Induced Thrombocytopenia

Background: Chemotherapy induced thrombocytopenia (CIT) is common, adversely impacts chemotherapy relative dose intensity, and may adversely impact cancer control. There is no approved therapy for CIT. In our recent phase II study of solid tumor patients with CIT (Soff et al, J. Clin. Onc., 2019), romiplostim lead to correction of platelet counts in 85% of participants within 3 weeks. While on romiplostim maintenance, only 6.8% of participants experienced chemotherapy dose reduction or delay as a result of recurrent CIT within a minimum of two cycles of chemotherapy or 8 weeks. However, there is a lack of long-term data on the efficacy and safety of romiplostim in CIT.Objectives: This is an extension analysis of the phase II study for patients receiving romiplostim maintenance for 12 months or longer.Patients/Methods: In the phase II study, 44 patients successfully met the primary endpoint of correction of their platelet count within 3 weeks and resumed chemotherapy with romiplostim maintenance. 21 patients (48%) remained on romiplostim for 12 months or longer. Data were collected from one month prior to initiation of romiplostim to one month after the last dose of drug. Data extracted included complete blood count, chemotherapy doses and dates, romiplostim doses and dates, body weight, cancer diagnosis, age, gender, date of death and thrombotic events. Efficacy was demonstrated by persistent maintenance of platelet counts during long-term chemotherapy and avoidance of episodes of reduced chemotherapy dose intensity. Safety was assessed by two methods: tracking the rates of venous or arterial thrombosis; as well as development of marrow fibrosis and/or secondary hematologic malignancy. The mean romiplostim doses and lab values are calculated by month of study participation.Results: All participants had metastatic disease. Breast (N=6) and colorectal (N=6) were the most common cancers. No participant discontinued romiplostim therapy due to an adverse event or futility. One patient received romiplostim at our institution, but chemotherapy at an outside hospital; details of his chemotherapy were not available for this analysis. 14 of the 20 (70%) of the analyzable participants experienced no episode of CIT; 4 subjects experienced a single chemotherapy dose delay due CIT. No patient experienced multiple delays in chemotherapy due to CIT. Two patients required a chemotherapy dose reduction.The mean monthly platelet counts remained controlled throughout the period of analysis. (Figure 1A). The mean romiplostim doses were in the range of 3-5 mcg/kg through 35 months. There were insufficient participants beyond month 36 to allow meaningful interpretation of platelet counts or mean romiplostim doses. There was no evidence of adverse impact on absolute neutrophil count or hemoglobin levels (Figure 1B). No patient developed leukoerythroblastic changes indicative of marrow fibrosis, and no cases of secondary hematologic malignancy were identified. Two participants experienced thrombosis. One individual experienced a deep vein thrombosis. A second participant with an established history of congenital thrombophilia, experienced multiple tumor associated infarctions. The thrombotic events did not lead to discontinuation of participation in the trial for either participant. Of the 44 patients in the phase 2 study who resumed chemotherapy, 21 were alive at 12 months (48%) and 12 were alive at 24 months (27%).Conclusions: In this long-term analysis, romiplostim was effective and safe in the treatment of CIT with no evidence of drug resistance, marrow fibrosis, or secondary hematologic malignancy. The rates of thrombosis were no higher than expected for this patient demographic. There are some limitations to our analysis which includes our inability to accurately capture non-parenteral chemotherapy (oral or investigational agents) which were excluded from our analysis. We are unable to assess an impact on overall survival or cancer progression. However, the fact that half the participants were alive at 12 months and a quarter at 24 months is a reassuring signal. The analysis also is limited to the patients who were eligible for the initial phase 2 trial and corrected their platelet count within 3 weeks. Within these limitations, the extension study provides reassurance for long-term efficacy and safety of romiplostim treatment for CIT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Romiplostim is approved to increase platelet counts in ITP and pre-surgery. We are describing the results of a clinical trial.

Assessing febrile neutropenia outcomes in patients receiving primary versus secondary prophylactic G-CSF treatment therapy with intermediate neutropenic risk chemotherapy regimens.

Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) reduce the severity and duration of chemotherapy-induced neutropenia. Currently, the use of G-CSF prophylactic treatment to prevent neutropenia and its complications varies widely in clinical practice with no standardization for intermediate-risk chemotherapy regimens. The purpose of this study was to assess neutropenic outcomes in patients receiving intermediate-risk chemotherapy regimens who receive primary versus secondary prophylactic G-CSFs. This is a retrospective, multicenter cohort study of patients who received intermediate risk chemotherapy regimens and at least one dose of G-CSF therapy. 121 patients were included and were divided into primary (n = 76) or secondary prophylaxis (n = 45) groups. The primary outcome for this study was the incidence of neutropenic episodes per course of treatment. The secondary outcomes included the percentage of patients who experienced delays in chemotherapy doses, the number of chemotherapy dose reductions, and the number of subsequent treatment delays. The incidence of neutropenic episodes over the course of therapy was 0.42 episodes in the primary group compared to 1.52 episodes in the secondary group (p < 0.05). 10.5% of patients in the primary group versus 54.3% of patients in the secondary group experienced chemotherapy dose delays (p < 0.05). There were no statistically significant differences in chemotherapy dose reductions or in the average number of FN risk factors between groups. This retrospective, cohort study determined that patients receiving intermediate risk chemotherapy regimens should receive primary prophylaxis, regardless of risk factors in order to decrease episodes of neutropenia and chemotherapy dose delays.

Затримка циклів та редукція дози хіміотерапії знижують ефективність лікування хворих на рак яєчників

Щорічно у всьому світі діагностується 205 тис. нових випадків раку яєчників (РЯ) та 125 тис. смертей від даної патології. Стандартним підходом до лікування пацієнток з III–IV стадіями епітеліального РЯ є первинна циторедукція з подальшою ад’ювантною хіміотерапією або неоад’ювантна хіміотерапія з подальшою циторедукцією. Численні дослідження продемонстрували безпеку і добру переносимість комбінованої паліативної хіміотерапії (ПХТ) на основі препаратів платини у пацієнток з РЯ, однак у частини пацієнток токсичність, викликана використанням хіміопрепаратів, призводить до затримки циклів та редукції доз ПХТ. У метааналізі, який провели Olawaiye і співавт. (2018 р.), оцінено вплив модифікації дози ПХТ на результат лікування пацієнток з РЯ. У дослідженні в групі пацієнток без модифікації доз ПХТ медіана безрецидивної виживаності становила 17,5 місяця, в той час як у пацієнток з модифікаціями доз ПХТ даний показник становив 9,9 місяця (р = 0,001). У пацієнток без модифікації доз ПХТ спостерігалася статистично значуща перевага за показником загальної виживаності (ЗВ) (48,0 проти 28,7 місяця у пацієнток з модифікаціями доз ПХТ) (р = 0,021). В іншому дослідженні в пацієнток, у яких затримка циклів спостерігалася 1 раз, медіана ЗВ становила 2,5 року, у жінок з 2 та більше затримками циклів медіана ЗВ становила 1,7 року (p = 0,03), в той час як у жінок без затримки доз даний показник становив 4,0 року (p = 0,02). І затримка з проведенням циклів ПХТ, і редукція доз хіміопрепаратів є факторами, здатними знижувати ефективність хіміотерапії. Необхідно уникати вищевказаних явищ для забезпечення ефективності хіміотерапії раку яєчників.

Sustainability and clinical outcomes of routine screening for pathogenic DPYD gene variants prior to fluoropyrimidine (FP) chemotherapy for gastrointestinal (GI) cancer.

216 Background: Dihyropyrimidine dehydrogenase (DPD) deficiency is present in 3-5% of patients, and is associated with substantially increased risk of severe and/or fatal toxicity during standard-dose FP chemotherapy. Genotyping of pathogenic DPYD variants is a readily available screening test for DPD deficiency, and prospective studies show that dose-reduced FP chemotherapy can be used safely in heterozygous DPYD variant carriers. Methods: Following a sentinel toxicity event the GI medical oncology group at the Norris Cotton Cancer Center adopted a shared practice of routine screening for pathogenic DPYD gene variants prior to FP chemotherapy (5-FU or capecitabine). Screening procedures involved physicians, NP/PAs, nurses, pharmacists, and schedulers. Testing was completed at a send-out lab until late 2020, when an in-house test became available. The current test panel evaluates for 3 gene variants: c.1905+1G &gt; A (*2A), c.1679T &gt; G (*13), and c.2846A &gt; T. We report on the sustainability and clinical outcomes of DPYD gene variant screening. We identified all patients starting new FP-containing intravenous chemotherapy regimens (e.g., FOLFOX, CAPOX) for treatment of GI cancer at two sites (LEB &amp; STJ) between Jan. 2019 and May 2021. We used electronic medical records to evaluate for completion of DPYD genotyping, and we describe the prevalence and management of DPYD gene variant carriers. Results: We identified 333 patients starting FP-containing chemotherapy regimens during the study period, including 287 patients without prior history of FP chemotherapy. Screening with DPYD genotyping was completed in 228 of 287 eligible patients (79%). Screening rates increased from 34% in Q1 of 2019 to 90% in Jan-May 2021. Five GI oncology sub-specialists accounted for 89% of screen-eligible patients and 96% of completed tests, but 10 unique physicians ordered ≥1 test. Of 228 screened patients, six (2.6%) were heterozygous carriers of pathogenic DPYD gene variants (*2A [2 patients], *13 [1], and c.2846A &gt; T [3]). Variant carriers started FP chemotherapy with a 33-50% reduction. Two of six patients required further dose reduction due to FP-related toxicity (grade 4 neutropenia, grade 3 diarrhea). All evaluable variant carriers completed planned initial treatment. Implementation challenges included variable insurance coverage of DPYD genotyping, site-specific test ordering and reporting processes, and inconsistent turn-around time for send-out testing (resolved with on-site testing). Conclusions: Routine screening for pathogenic DPYD gene variants prior to FP chemotherapy is feasible and sustainable in the U.S. DPYD genotyping coupled with chemotherapy dose reductions for DPYD variant carriers facilitates safe and timely completion of planned chemotherapy treatments.