Carboplatin Paclitaxel Research Articles

Efficacy and Adverse Reactions of Carboplatin, Nab-Paclitaxel Regimen Combined with Atezolizumab in the Treatment of Non-Small Cell Lung Cancer

We attempt to study the efficacy and adverse reactions of carboplatin, nab-paclitaxel regimen combined with atezolizumab in non-small cell lung cancer treatment. We randomly selected 120 non-small cell lung cancer patients who received therapy in our hospital from January 2019 to December 2021 and divided them into two groups, 60 cases respectively. Treated control group with carboplatin and paclitaxel combined with pembrolizumab, while observation group with carboplatin and albumin paclitaxel combined with pembrolizumab. Compared both groups on the efficacy, incidence of adverse reactions, levels of peripheral blood lymphocyte subsets and serum tumor markers. After treatment, observation group possessed higher objective remission rate and disease control rate than control group (p<0.05); observation group had lower adverse reactions rate during the treatment period than control group (p<0.05); observation group had higher cluster of differentiation 3+, cluster of differentiation 4+ and cluster of differentiation 4+/cluster of differentiation 8+ values than control group, but it possessed lower cluster of differentiation 8+ values than control group (p<0.05). Observation group had lower cytokeratin 19 fragment antigen 21-l, squamous cell carcinoma antigen, carbohydrate antigen 125 and carcinoembryonic antigen levels than control group (p<0.05). Carboplatin, nab-paclitaxel regimen combined with atezolizumab in treating non-small cell lung cancer patients can effectively alleviate and control their disease, reduce the risk of adverse reactions during the treatment process and improve the body’s immune function, which is worthy of promotion.

Pre-operative Carboplatin/Paclitaxel Versus 5-Fluorouracil (5-FU)-based Chemoradiotherapy for Older Adults With Esophageal Cancer

This study aimed to compare the efficacy and tolerability of pre-operative platinum/5-fluorouracil (P5F) and carboplatin/paclitaxel (CP), in combination with radiation therapy in older adults with locally advanced, stage I-III esophageal cancer. We retrospectively reviewed 51 patients aged ≥70 years who underwent chemoradiotherapy followed by esophagectomy for stage I-III esophageal cancer between 2008 and 2018. Pathological complete response (pCR) and survival rates were compared across the two chemotherapy regimen arms. Treatment completion (p=0.28), pCR (p=0.89), and partial response rates were similar across both chemotherapy groups. Overall survival (OS) and disease-free survival (DFS) were similar across both groups with HR=0.80 (p=0.62) and HR=0.72 (p=0.72) respectively. The lesser toxic CP regimen may be used in older patients with locally advanced esophageal cancer, with tumor response and survival rates similar to P5F chemotherapy.

Neo-Adjuvant Chemotherapy Reduces, and Surgery Increases Immunosuppression in First-Line Treatment for Ovarian Cancer.

Simple SummaryThe immune system plays an important role in the development and progression of cancer. The current treatments for ovarian cancer (surgery and chemotherapy) create changes in the immune system, but it is not clear how. Nevertheless, if immunotherapy is associated on top of this, then it seems crucial to understand what is changing in the current state of the art. In this study, we measured immune-related proteins in the serum of ovarian cancer patients throughout their treatment. We discovered that carboplatin–paclitaxel as a chemotherapeutic treatment reduces immunosuppression and promotes immunostimulation, meaning that the immune system be-comes less hostile and more in favour of the patient. Therefore, chemotherapy seems to induce a temporary window of opportunity to insert immunotherapy during the current treatment of ovarian cancer patients.In monotherapy, immunotherapy has a poor success rate in ovarian cancer. Upgrading to a successful combinatorial immunotherapy treatment implies knowledge of the immune changes that are induced by chemotherapy and surgery. Methodology: Patients with a new ovarian cancer diagnosis underwent longitudinal blood samples at different time points during primary treatment. Results.: Ninety patients were included in the study (33% primary debulking surgery (PDS) with adjuvant chemotherapy (ACT), 61% neo-adjuvant chemotherapy (NACT) with interval debulking surgery (IDS), and 6% debulking surgery only). Reductions in immunosuppression were observed after NACT, but surgery reverted this effect. The immune-related proteins showed a pronounced decrease in immune stimulation and immunosuppression when primary treatment was completed. NACT with IDS leads to a transient amelioration of the immune microenvironment compared to PDS with ACT. Conclusion: The implementation of immunotherapy in the primary treatment schedule of ovarian cancer cannot be induced blindly. Carboplatin–paclitaxel seems to ameliorate the hostile immune microenvironment in ovarian cancer, which is less pronounced at the end of primary treatment. This prospective study during primary therapy for ovarian cancer that also looks at the evolution of immune-related proteins provides us with an insight into the temporary windows of opportunity in which to introduce immunotherapy during primary treatment.

Natural History of Paclitaxel-associated Acute Pain Syndrome: A Case Report of Rare Side Effect of Paclitaxel

BACKGROUND: One of the harshest side effects following anticancer agent treatments is chemotherapy-induced neuropathic pain. After surgical staging, chemotherapy combination of paclitaxel carboplatin could be a choice of therapy for Stage II or more advanced stage of ovarian cancer. Different side effects may appear after the application of paclitaxel. CASE REPORT: Here, we show an uncommon case of paclitaxel-acute pain syndrome (P-APS), and how we deal with such cases according to our experiences. One uncommon side effect is P-APS, which can be treated effectively with the administration of non-steroidal anti-inflammatory drugs, corticosteroid, and supportive therapy. CONCLUSION: One uncommon side effect of Paclitaxel induced neuropathic can be treated effectively with the administration of non-steroidal anti inflammatory drugs, corticosteroid, and supportive therapy.

Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response

BackgroundThe prognosis of high grade serous ovarian cancer (HGSOC) patients is closely related to the immune microenvironment and immune response. Based on this, the purpose of this study was to construct a model to predict chemosensitivity and prognosis, and provide novel biomarkers for immunotherapy and prognosis evaluation of HGSOC.MethodsGSE40595 (38 samples), GSE18520 (63 samples), GSE26712 (195 samples), TCGA (321 samples) and GTEx (88 samples) were integrated to screen differential expressed genes (DEGs) of HGSOC. The prognosis related DEGs (DEPGs) were screened through overall survival analysis. The DEGs-encoded protein–protein interaction network was constructed and hub genes of DEPGs (DEPHGs) were generated by STRING. Immune characteristics of the samples were judged by ssGSEA, ESTIMATE and CYBERSORT. TIMER was used to analyze the relationship between DEPHGs and tumor-infiltrating immunocytes, as well as the immune checkpoint genes, finally immune-related DEPHGs (IDEPHGs) were determined, and whose expression in 12 pairs of HGSOC tissues and tumor-adjacent tissues were analyzed by histological verification. Furthermore, the chemosensitivity genes in IDEPHGs were screened according to GSE15622 (n = 65). Finally, two prediction models of paclitaxel sensitivity score (PTX score) and carboplatin sensitivity score (CBP score) were constructed by lasso algorithm. The area under curve was calculated to estimate the accuracy of candidate gene models in evaluating chemotherapy sensitivity.Results491 DEGs were screened and 37 DEGs were identified as DEPGs, and 11 DEPHGs were further identified. Among them, CXCL13, IDO1, PI3, SPP1 and TRIM22 were screened as IDEPHGs and verified in the human tissues. Further analysis showed that IDO1, PI3 and TRIM22 could independently affect the chemotherapy sensitivity of HGSOC patients. The PTX score was significantly better than TRIM22, PI3, SPP1, IDO1 and CXCL13 in predicting paclitaxel sensitivity, so was CBP score in predicting carboplatin sensitivity. What’s more, both of the HGSOC patients with high PTX score or high CBP score had longer survival time.ConclusionsFive IDEPHGs identified through comprehensive bioinformatics analysis were closely related with the prognosis, immune microenvironment and chemotherapy sensitivity of HGSOC. Two prediction models based on IDEPHGs might have potential application of chemotherapy sensitivity and prognosis for patients with HGSOC.

Peripherally-driven myeloid NFkB and IFN/ISG responses predict malignancy risk, survival, and immunotherapy regime in ovarian cancer

BackgroundTumors can influence peripheral immune macroenvironment, thereby creating opportunities for non-invasive serum/plasma immunobiomarkers for immunostratification and immunotherapy designing. However, current approaches for immunobiomarkers’ detection are largely quantitative, which is unreliable...

3-Weekly Paclitaxel-Carboplatin With Radical Radiation for Stage III NSCLC – An Option During COVID-19 Pandemic

Purpose/Objective(s)The optimal choice and schedule of chemotherapy (CT) given concurrently with radiation (RT) for primary treatment of stage III unresectable non-small cell lung cancer (NSCLC) remain debatable. 3-weekly paclitaxel-carboplatin (PC) is a convenient schedule but not well studied. This study aims to review the efficacy, toxicities and prognostic factors for treatment outcomes of this regime.Materials/MethodsPatients with unresectable stage III (AJCC TNM 7th edition) NSCLC who underwent 3-weekly PC (P 175mg/m2, C AUC = 5 on day 1 of 21-day cycle) concurrent with radical RT from January 2007 to April 2017 were retrospectively reviewed. RT was given 5 days per week in 2 Gy daily fractions to the planning target volume using 3D-conformal technique. Total of 4 to 6 cycles of CT were allowed at clinicians’ discretion. Patients who had > 2 CT cycles before RT, < 1 cycle of CT concurrently with RT and total RT dose < 60 Gy were excluded.ResultsA total of 65 patients with median age 63 years (range 45-74 years) were included. Distribution of staging was similar between stage IIIA (53.8%) and stage IIIB (46.2%). Majority (41.5%) of patients had adenocarcinoma, followed by squamous histology (38.5%). Most patients received 60 Gy of RT (96.9%) and 4 cycles of CT (83.1%). At a median follow up of 29.5 months (mo) (Interquartile range 13.4-53.6 mo), the median overall survival (OS) was 35.0 mo (95% CI 17.5-52.4 mo) and the median progressive free survival (PFS) was 12.2 mo (95% CI 8.7-15.8 mo). The 1, 3 and 5-year OS rates were 76.9%, 48.3% and 29.7% respectively. Multivariate analyses showed that gross tumor volume (HR 1.005 [95% CI 1.002-1.008]; P < 0.01), mean heart dose ≥ 5 Gy (HR 2.507 [95% CI 1.293-5.108]; P < 0.01) and more than 4 cycles of CT given (HR 3.830 [95% CI 1.479-9.921]; P < 0.01) were independent prognostic factors for worse OS, while ≥ grade 2 esophagitis was an independent prognostic factor for worse PFS (HR 2.563 [95% CI 1.031-6.370]; P = 0.04). The maximum grade toxicity was grade 2 in 20 patients (41.5%), grade 3 in 27 patients (20.0%) and grade 4 in 5 patients (7.7%). No grade 5 events were observed. The most common grade 3 or 4 toxicity was neutropenia, which occurred in 9 (13.8%) and 5 (7.7%) patients respectively. Neutropenic fever was seen in 3 patients (4.6%). Grade 2 or above pneumonitis and esophagitis occurred in 5 (7.7%) and 9 (13.8%) patients respectively.ConclusionThe present study is the largest to date reviewing radical chemoradiotherapy using 3-weekly TC for unresectable stage III NSCLC. Being well tolerated with comparable outcomes to historical data, it is a preferred option during the COVID-19 pandemic due to less hospital visits. Prospective studies evaluating whether this regime in combination with more sophisticated RT techniques could further improve the therapeutic ratio in the era of consolidative durvalumab are warranted.

Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience

BackgroundFavorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. MethodsA phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30–50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). Results91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). ConclusionRisk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.

Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer

PurposeInsulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. DesignPatients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. Results170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82–1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). ConclusionAddition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.

IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain

IntroductionFinal overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase 3 IMpower150 study (NCT02366143) evaluating atezolizumab plus bevacizumab plus carboplatin and paclitaxel (ABCP) or atezolizumab plus carboplatin and paclitaxel (ACP) versus bevacizumab plus carboplatin and paclitaxel (BCP). MethodsOverall, 1202 patients (intention-to-treat population) with chemotherapy-naive, metastatic, nonsquamous NSCLC were randomized to ABCP, ACP, or BCP. Patients with treated, stable brain metastases were permitted. OS was evaluated in EGFR mutations and baseline liver metastases subgroups; rate and time to development of new brain metastases were evaluated in the intention-to-treat patients. ResultsAt data cutoff (September 13, 2019; median follow-up, 39.3 mo), OS improvements were sustained with ABCP versus BCP in sensitizing EGFR mutations (all: hazard ratio [HR] = 0.60; 95% confidence interval [CI]: 0.31–1.14; previous tyrosine kinase inhibitor [TKI]: HR = 0.74; 95% CI: 0.38–1.46) and baseline liver metastases (HR = 0.68; 95% CI: 0.45–1.02) subgroups. ACP did not have survival benefit versus BCP in sensitizing EGFR mutations (all: HR = 1.0; 95% CI: 0.57–1.74; previous TKI: HR = 1.22; 95% CI: 0.68–2.22) or liver metastases (HR = 1.01; 95% CI: 0.68–1.51) subgroups. Overall, 100 patients (8.3%) developed new brain metastases. Although not formally evaluated, an improvement toward delayed time to development was found with ABCP versus BCP (HR = 0.68; 95% CI: 0.39–1.19). ConclusionsThis final exploratory analysis revealed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with previous TKI failures, and with liver metastases, although these results should be interpreted with caution. The impact of ABCP on delaying the development of new brain lesions requires further investigation.

Bevacizumab Combined with Platinum–Taxane Chemotherapy as First-Line Treatment for Advanced Ovarian Cancer: Results of the NOGGO Non-Interventional Study (OTILIA) in 824 Patients

Simple SummaryThe OTILIA non-interventional study aimed to assess the safety and effectiveness of a standard treatment regimen for advanced ovarian cancer in Germany. All of the women participating in the study received chemotherapy combined with a targeted treatment called bevacizumab. Among the 824 women who received treatment in this study, the median duration of progression-free survival (time alive without their disease returning) was 19.4 months. This is similar to the results in previous randomized phase 3 trials in more restricted populations of women. The safety and effectiveness of treatment seemed to be similar in older (at least 70 years) and younger (less than 70 years) women. Quality of life improved over time.In the single-arm non-interventional OTILIA study, patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IIIB–IV ovarian cancer received bevacizumab (15 mg/kg every 3 weeks for up to 15 months) and standard carboplatin–paclitaxel. The primary aim was to assess safety and progression-free survival (PFS). Subgroup analyses according to age were prespecified. The analysis population included 824 patients (453 aged <70 years, 371 aged ≥70 years). At data cutoff, the median bevacizumab duration was 13.8 months. Grade ≥3 adverse events (AEs), serious AEs, and AEs leading to bevacizumab discontinuation were more common in older than younger patients, whereas treatment-related AEs were less common. Median PFS was 19.4 months, with no clear difference according to age (20.0 vs. 19.3 months in patients <70 vs. ≥70 years, respectively). One-year OS rates were 92% and 90%, respectively. Mean change from baseline in global health status/quality of life showed a clinically meaningful increase over time. In German routine oncology practice, PFS and safety were similar to reported randomized phase 3 bevacizumab trials in more selected populations. There was no notable reduction in effectiveness and tolerability in patients aged ≥70 years; age alone should not preclude use of bevacizumab-containing therapy. ClinicalTrials.gov: NCT01697488.

Current Treatment Strategies for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia.

Simple SummaryInterstitial pneumonia is a poor prognostic comorbidity in patients with non-small-cell lung cancer. No matter how effective the treatment for lung cancer is, once an acute exacerbation of pre-existing interstitial pneumonia occurs, it will be fatal to the patient at a high rate. Therefore, it is important to choose a therapy that is unlikely to induce acute exacerbation of interstitial pneumonia. In this review article, we summarize the current evidence on pharmacotherapy, surgery and perioperative treatment, and radiation therapy for non-small-cell lung cancer with comorbid interstitial pneumonia, and discuss future perspectives.Of patients with advanced non-small-cell lung cancer (NSCLC), 5–10% have interstitial pneumonia (IP) at the time of diagnosis. To avoid fatal acute exacerbations of pre-existing IP, appropriate patient selection and low-risk treatment choices are warranted. Risk factors for acute exacerbation of pre-existing IP with cytotoxic drugs include honeycomb lungs on computed tomography (CT) and low forced vital capacity, but risk factors with immune checkpoint inhibitors (ICIs) have not been fully investigated. For advanced or recurrent NSCLC with comorbid IP, carboplatin plus nanoparticle albumin-bound paclitaxel is the standard of care for first-line treatment, but second-line or later treatment has not been established. ICI holds great promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Since the indications for pharmacotherapy and radiotherapy for NSCLC with comorbid IP are quite limited, surgical resection should be considered as much as possible for patients with operable stages. A scoring system has been reported to predict the risk of postoperative acute exacerbation of pre-existing IP, but perioperative treatment has not been established. In the future, it is necessary to accumulate more cases and conduct further research, not only in Japan but also worldwide.

Characterization of patients with BRCA mutated ovarian cancer who are eligible versus not eligible for PARP inhibitor maintenance therapy: exploratory analysis of the VELIA study

<h3>Objectives:</h3> Previous phase 3 trials of front-line maintenance with the PARP inhibitors (PARPi) olaparib and niraparib only included patients (pts) with complete (CR) or partial (PR) response following front-line chemotherapy (CT); both agents were adopted as standard of care (SOC) in these pts. This prevented the systematic study of all pts who are eligible for PARPi maintenance therapy after front-line CT or to predict their responses. The phase 3 VELIA study (NCT02470585) added veliparib (VEL) to front-line CT at diagnosis, followed by VEL maintenance in the absence of progressive disease (PD), permitting treatment of a broader cohort of pts. This exploratory analysis evaluated baseline characteristics associated with first-line CT response, to understand if predictive variables exist that could identify those who would be eligible vs ineligible for SOC PARPi maintenance. <h3>Methods:</h3> Pts with untreated Stage III/IV ovarian cancer were randomized to carboplatin/paclitaxel (CP) + placebo (PBO) followed by PBO maintenance (control arm), CP + VEL followed by PBO maintenance (VEL combination only), or CP + VEL followed by VEL maintenance (VEL throughout). Pts without progression after combination treatment transitioned to assigned maintenance therapy. In this exploratory analysis, pts with germline or somatic <i>BRCA</i> mutations (BRCAm) were grouped as maintenance eligible (ME; with CR/PR or non-PD with surgical complete resection) or maintenance not eligible (MNE; with stable disease/progression/non-CR/non-PD). Progression-free survival (PFS) in pts starting maintenance was measured from initiation of maintenance treatment. <h3>Results:</h3> Of 1,140 randomized pts, 298 had germline or somatic <i>BRCA</i>m; of these, 278 could be classified according to maintenance eligibility. MNE pts (n=56) were distributed equally among the control, VEL combination only, and VEL throughout arms (21%, 19%, and 21% of evaluable pts, respectively). MNE subgroups were enriched for advanced disease (18-39% of MNE subgroups vs 13-19% of ME subgroups had Stage IV disease) and less favorable performance status (41-67% MNE vs 20-40% of ME pts had ECOG performance status ≥1). For ME pts (n=222), median PFS from initiation of maintenance was not reached in the VEL throughout arm vs 19.7 months in the control arm (HR 0.29, 95% CI 0.16-0.52, Figure). For MNE pts, median PFS was 16.4 months in the VEL throughout arm and 18.9 months in the control arm (HR 1.331, 95% CI 0.52-3.44); however, sample sizes (n=18 and n=16, respectively) limit a meaningful analysis of PFS in these pts. <h3>Conclusions:</h3> The results of this exploratory analysis suggest that VEL has robust efficacy in pts with BRCA-mutated tumors eligible for SOC PARPi maintenance. Baseline characteristics of advanced disease and less favorable performance status were more common in MNE pts than ME pts. Molecular characterization is ongoing to identify mechanisms of sensitivity that predict eligibility for, and response to, PARPi therapy.

PO-1174 3-weekly paclitaxel-carboplatin with radiation for stage III NSCLC – option during COVID-19 pandemic

Purpose or Objective: The optimal choice and schedule of chemotherapy (CT) given concurrently with radiation (RT) for primary treatment of stage III unresectable non-small cell lung cancer (NSCLC) remain debatable. 3-weekly paclitaxelcarboplatin (PC) is a convenient schedule but not well studied. This study aims to review the efficacy, toxicities and prognostic factors for treatment outcomes of this regime. Materials and Methods: Patients with unresectable stage III (AJCC TNM 7th edition) NSCLC treated with radical chemoradiotherapy using 3-weekly PC (P 175mg/m2, C AUC=5 on day 1 of 21-day cycle) from January 2007 to April 2017 were retrospectively reviewed. RT was given 5 days per week in 2 Gy daily fractions to the planning target volume using 3D-conformal technique. Total of 4 to 6 cycles of CT were allowed at clinicians’ discretion. Patients who had >2 CT cycles before RT, <1 cycle of CT concurrently with RT and total RT dose < 60 Gy were excluded. Results: A total of 65 patients with median age 63 years (range 45-74 years) were included. Stage distribution was similar between IIIA (53.8%) and IIIB (46.2%). Majority (41.5%) of patients had adenocarcinoma, followed by squamous histology (38.5%). Most patients received 60 Gy of RT (96.9%) and 4 cycles of CT (83.1%). At a median follow up of 29.5 months (mo) (Interquartile range 13.4-53.6 mo), the median overall survival (OS) was 35.0 mo (95% CI 17.5-52.4 mo) and the median progressive free survival (PFS) was 12.2 mo (95% CI 8.7-15.8 mo). The 1, 3 and 5-year OS rates were 76.9%, 48.3% and 29.7% respectively. Multivariate analyses showed that gross tumour volume (HR 1.005 [95% CI 1.002-1.008];p<0.01), mean heart dose ≥ 5 Gy (HR 2.507 [95% CI 1.293-5.108];p< 0.01) and more than 4 cycles of CT given (HR 3.830 [95% CI 1.479-9.921];p <0.01) were independent prognostic factors for worse OS, while ≥ grade 2 esophagitis was an independent prognostic factor for worse PFS (HR 2.563 [95% CI 1.031-6.370];p=0.04). The maximum grade toxicity was grade 2 in 20 patients (41.5%), grade 3 in 27 patients (20.0%) and grade 4 in 5 patients (7.7%). No grade 5 events were observed. The most common grade 3 or 4 toxicity was neutropenia, which occurred in 9 (13.8%) and 5 (7.7%) patients respectively. Neutropenic fever was seen in 3 patients (4.6%). Grade 2 or above pneumonitis and esophagitis occurred in 5 (7.7%) and 9 (13.8%) patients respectively. (Figure Presented) Conclusion: Radical chemoradiotherapy using 3-weekly PC for unresectable stage III NSCLC is well tolerated, with comparable outcomes to historical data and less hospital visits which is preferred during the COVID-19 pandemic. Prospective studies evaluating whether this regime in combination with more sophisticated RT techniques to lower the cardiac and esophageal doses could improve the survival outcomes and further enhance the therapeutic ratio in the era of consolidative durvalumab are warranted.

Dose-dense Paclitaxel and Carboplatin as Neoadjuvant Chemotherapy for Stage IIB/IIIA Non-small Cell Lung Cancer – A Phase II trial

AimsThe approach to potentially resectable non-small cell lung cancer (NSCLC) remains controversial. There is a benefit of neoadjuvant chemotherapy (NACT), but the ideal regimen is unknown. We evaluated the efficacy and safety of dose-dense NACT in potentially resectable NSCLC in this phase II trial. Materials and methodsPaclitaxel at 80 mg/m2 on days 1, 8 and 15 with AUC-6 carboplatin on day 1, 3 weekly for four cycles was evaluated as NACT. Patients with Eastern Cooperative Oncology Group performance status 0–2, stage IIB and IIIA (with only non-bulky N2 nodes) were included. The primary end point was the objective response rate. Secondary end points included toxicity, progression-free survival, recurrence-free survival, complete resection rate and overall survival. The relative dose intensity (RDI) was calculated to define tolerability (CTRI/2016/05/006916). ResultsIn total, 37 patients were enrolled (median age 55 years). Most (78.8%) were smokers. Most patients had adenocarcinoma (57.6%) and stage IIIA disease (81.0%) according to the seventh American Joint Committee on Cancer staging system. Seventy-eight per cent of patients completed four cycles. The objective response rate was 75.6% with a complete response in 10.8%. The mean RDI of paclitaxel was 88.61%, with 68.0% of patients able to maintain an RDI ≥85.0%. In total, 187 toxicity events were recorded (120 grade 1, 64 grade 2 and three grade 3 events). Common toxicities were peripheral neuropathy (20.3%), myalgia (19.8%), nausea (15.7%) and neutropenia (10.2%). There were no treatment-related deaths. Seventeen patients underwent surgery (lobectomy 82.4%). After a median follow-up of 47 months (95% confidence interval 27–50.7 months), the median progression-free survival was 9.6 months (7.4–17.4) and overall survival was 29.2 months (16.0–37.2). ConclusionDose-dense paclitaxel–carboplatin is feasible, safe and efficacious and should be evaluated further in potentially resectable NSCLC.

Treatment of advanced-stage ovarian cancer including combination of intra-abdominal chemotherapy

Introduction.Ovarian cancer is the leading cause of death from gynecological malignancies: the one-year relative survival rate with stages 3 and 4 of the disease is 20%. The results of treatment remain unsatisfactory, which dictates the need to find new methods of treatment. The aim of the study was to evaluate the effectiveness of the use of HIIH (hyperthermic intraperitoneal intraoperative chemoperfusion, HIPEC) in patients with the diagnosis of: ovarian cancer IIIA-From the stage of the disease.Materials and methods.117 cases of stage IIIA-C ovarian cancer treated at the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine from January 2014 to March 2021 were retrospectively studied. All patients underwent 3 cycles of neoadjuvant chemotherapy (NAPHT) according to the paclitaxel+carboplatin (PCb) scheme, followed by surgical treatment to the extent of maximum cytoreductive surgery. Two study groups were formed: 1 — cases with GIIH (N=57), 2-without GIIH (N=60). On the 14-16 day after the operation, all patients underwent 3 cycles of adjuvant chemotherapy according to the PCb scheme.Results.A significant increase in overall survival was found in the first group of patients with HIPEC. This technique allows to increase the survival rate of patients for 14 months at stage IIIA-B (p&lt;0.05). At stage IIIC, there was no statistically significant difference in the survival rate of patients. There was a tendency to increase the survival rate by 5 months (p&gt;0.05), which is associated with the pronounced prevalence of the tumor process and the technical impossibility of removing the tumor. Discussion.The concentration of drugs in the abdominal cavity and in the blood plasma significantly differs due to the functioning of the peritoneal-plasma barrier, which leads to a lower toxicity in comparison with systemic chemotherapy, and therefore allows you to give a large dose of the drug with fewer adverse events, and the fact of hyperthermia (42°C) has a positive effect on the effectiveness of intraperitoneal chemotherapy. To date, this method has not been included in the clinical recommendations on the territory of the Russian Federation, but data from foreign literature, including randomized trials, have shown the high effectiveness of this method.Conclusion.The results obtained in the course of our study demonstrate the effectiveness of this technique, in the form of an increase in overall and relapse-free survival with acceptable toxicity.

Efficacy and safety of first-line veliparib and carboplatin–paclitaxel in patients with HER2− advanced germline BRCA+ breast cancer: Subgroup analysis of a randomised clinical trial

BackgroundAddition of veliparib to carboplatin–paclitaxel, with continuation of veliparib monotherapy if carboplatin–paclitaxel was discontinued, improved progression-free survival (PFS) in patients with germline BRCA-associated locally advanced/metastatic HER2− breast cancer and ≤2 lines of previous cytotoxic therapy for metastatic disease in BROCADE3. A pre-planned subgroup analysis evaluated efficacy and safety in patients without previous cytotoxic therapy for metastatic disease. MethodsPatients were randomised 2:1 to receive veliparib (120 mg orally BID) or placebo on days −2 to 5. Carboplatin (AUC 6) was administered on day 1, and paclitaxel (80 mg/m2) on days 1, 8 and 15 (21-day cycles). Patients discontinuing carboplatin–paclitaxel for reasons besides progression could continue veliparib/placebo monotherapy (300 mg BID, increasing to 400 mg BID if tolerated) until progression. The primary end-point was PFS assessed by investigator. ResultsOf 509 patients in the intention-to-treat population (98.6% female; mean age 47, standard deviation 11), 413 (81%) had no previous cytotoxic therapy for metastatic disease (274, veliparib; 139, placebo). In the first-line subgroup, median PFS was 16.6 months (95% confidence interval [CI] 13.4–18.7) versus 13.1 months (95% CI 11.4–14.5) for the veliparib versus control groups (hazard ratio 0.70, 95% CI 0.54–0.89, P = .004). More patients were alive and progression-free at 2 years (36% versus 23.2%) and 3 years (27.9% versus 13.3%) in the veliparib versus control group. Adverse events unrelated to progression leading to study drug discontinuation occurred in 25 (9.1%) and 8 (5.8%) patients. ConclusionsVeliparib with carboplatin–paclitaxel led to durable disease control among first-line patients, suggesting a benefit of this treatment approach in early lines. Clinical trial registrationNCT02163694.

Multimodal Treatment of Primary Advanced Ovarian Cancer.

Epithelial ovarian cancer is the second most common malignancy of the female genital tract, with approximately 7,400 new cases annually in Germany. With 5,500 deaths per year, ovarian cancer is the leading gynecologic cause of death. Epithelial ovarian cancer is characterized by morphologic heterogeneity with 4 molecular biological subtypes (immunoreactive-like, differentiated-like, proliferative-like, mesenchymal-like) with different prognosis. Significantly improved survival is achieved by optimal debulking with no residual disease (R0). Systematic lymphonodectomy of clinical negative lymph nodes has no effect on overall survival in advanced ovarian cancer. Interval debulking in advanced ovarian cancer after three cycles of neoadjuvant chemotherapy with carboplatin/paclitaxel is controversial. Standard chemotherapy for advanced ovarian cancer consists of six cycles of carboplatin AUC5 and paclitaxel 175 mg/m2, in a three-week cycle. Intraperitoneal chemotherapy is not a standard therapy. Anti-hormonal therapy with an aromatase inhibitor plays a minor role in therapy of both low grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC). A major achievement in ovarian cancer therapy has been the results of the SOLO-1 trial, in which olaparib as a first line maintenance monotherapy resulted in an overall 70% lower risk of disease progression in patients with advanced Breast Cancer Gene (BRCA)-mutated ovarian cancer.

Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers: State of art and an innovative approach for prevention.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that occurs in 20% of ovarian cancer patients treated with the combination of carboplatin/paclitaxel (CP). This toxicity is directly correlated with the dose of paclitaxel administered. Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate, but, unfortunately, no significant improvement was obtained. CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment. Neuropathy can last for months and even years after its onset. Moreover, patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs, and residual neuropathy can affect the continuation of treatment. There are no approved drugs that mitigate or prevent the onset of CIPN. In this review, we summarize the evidence regarding the incidence of CIPN with different taxane formulations, regimen schedules and prevention systems. In particular, the Hilotherm® Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries. We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN. Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated; only two patients (4.5%) stopped hilotherapy because of cold intolerance, and only one patient (2.2%) experienced grade ≥ 2 CIPN.

Feasibility of an adapted schedule of carboplatin plus paclitaxel in elderly women with advanced ovarian cancer: A retrospective cohort.

5546 Background: The EWOC-1 trial compared Carboplatin monotherapy (C mono) to two different Carboplatin + Paclitaxel (CP) regimens (weekly or 3-weekly) in vulnerable elderly patients treated for advanced ovarian cancers (OC). This study was closed prematurely because of a worse outcome in the C mono group. Both CP regimens were equivalent in terms of feasibility and efficacy with different toxicity profiles. Optimal CP regimen in elderly patient is still unknown. Here we propose a study of another adapted regimen of CP (aCP) performed in elderly patients in our institution. Methods: We retrospectively analyzed OC patients ≥ 70 years who received a Carboplatin AUC 4-5 d1q3week + Paclitaxel 80 mg/m² d1-d8 q3week regimen between 2015 and 2019. Primary endpoint was treatment feasibility according to the EWOC-1 standard: completion of 6 courses of chemotherapy without early stopping for disease progression, death or unacceptable toxicity (adverse event (AE) related to chemotherapy or treatment procedure leading either to early treatment stopping, to an unplanned hospital admission or to death or to a dose delay lasting more than 14 days or more than 2 dose reductions). Results: We identified 36 pts with a median age of 79 years (table). All patient but one had an ONCODAGE-G8 score ≤ 14, 30.6% of patients had a comorbidity Charlson’s index &gt; 4 and 52.5% had an albumin rate &lt; 35 g/L. The feasibility endpoint was met in 58.3% of patients (IC95% = [25.6; 57.8]). Main causes of treatment failure (TF) were early discontinuation because of toxicity in 6 patients (16.7%) and progressive disease in 3 patients (8.33%). Median PFS was 35.3 months (IC95% = [22.7; NR]) and median OS was 62.1 months (IC95% = [31.4.0; NR]). The most frequent AE were asthenia (all grades = 94.4%, grade 3-4 = 13.9%), anemia (all grades = 94.4%, grade 3-4 = 27.8%), neutropenia (all grades = 66.7%, grade 3-4 = 38.9%) and neuropathy sensory (all grades = 61.1%, no grade 3-4). Non high-grade-serous histological type and a poor Charlson’s score were associated with a higher rate of TF (100% and 63.6%, respectively). Conclusions: These results are consistent with the findings of the EWOC-1 trial in both CP regimens and suggest that aCP could be non-inferior with an acceptable toxicity profile. Further prospective and comparative studies are mandatory to confirm this trend and to better identify predictive factors of TF in OC elderly patients.[Table: see text]