Platinum-free Regimens Research Articles

Second-line treatment outcomes after first-line chemotherapy plus immunotherapy in Extensive-Stage small cell lung cancer (ES-SCLC) patients: A large French multicenter study

IntroductionChemotherapy combined with immunotherapy (CT-IO) is the standard treatment for patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC). This study evaluates the effectiveness of second-line (2L) following CT-IO. Patients and MethodsAll patients from 10 centers who received a 2L after a first-line CT-IO were included. They were divided into 3 groups: platinum-based, lurbinectedin or others (topotecan, CAV, taxanes). We assessed overall survival (OS) and 2L progression-free survival (2L-PFS) according to treatment and platinum free-interval (PFI) < or ≥ 90 days. ResultsAmong 82 patients included, median age was 67.0 years, 29.3 % had a Performans Status ≥ 2, 36.6 % had brain progression, 69.5 % were considered “platine-sensitive” and 30.5 % “platine-resistant” (PFI ≥ or < 90 days, respectively). As 2L, 37/82 patients (45.1 %) received platinum-doublet, 21/82 (25.6 %) lurbinectedin and 24/82 (29.3 %) others. Patients with a PFI ≥ 90 days received mainly platinum-based rechallenge (34/57, 59.6 %). With a median follow-up of 18.5 months, the median OS was 5.0 months (95 %CI, 1.5–7.9) / 6.8 months (95 %CI, 5.5–8.7) for platinum-resistant / sensitive, respectively (log rank p = 0.017). The median 2L-PFS was 1.9 months (95 %CI, 1.2–4.7) / 3.9 months (95 %CI, 2.9–6.0) for platinum-resistant / sensitive, respectively. Median OS was 8.1 (95 %CI, 6.3–12.9) / 4.9 (95 %CI, 3.7–6.8) / 5.1 months (95 %CI, 2.5–7.8) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.017). Median 2L-PFS was 4.6 (95 %CI, 3.9–7.2) / 2.7 (95 %CI, 1.6–3.9) / 2.2 months (95 %CI, 1.5–4.1) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.025). DiscussionPlatinum-based rechallenge after a first-line CT-IO showed promising results despite particularly unfavorable characteristics within our real-word population. Lurbinectedin when used after IO demonstrated as low efficacy as other platinum-free regimens.

Efficacy of second-line chemotherapy or immune checkpoint inhibitors for patients with a prolonged objective response (≥ 6 months) after first-line therapy for recurrent or metastatic head and neck squamous cell carcinoma: a retrospective study

BackgroundPatients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors (ICIs) are effective in patients with tumor progression < 6 months following first-line, platinum-based chemotherapy (PBC), but data are missing for patients with progression ≥ 6 months after the last platinum dose.MethodsRetrospective analysis (six French centers, 2008–2019) of all consecutive R/M-HNSCC patients. treated first-line with PBC and tumor progression ≥ 6 months after the last platinum dose. Primary endpoint: progression-free survival after second-line therapy (PFS2). Additional endpoints: overall survival from Day 1 of first-line (OS1) and second-line (OS2) therapy.ResultsR/M-HNSCC patients (n = 144) received cisplatinum (n = 67, 47%) or carboplatinum (n = 77, 53%) first-line. Response after first-line: complete response (CR; n = 16, 11%); partial response (PR; n = 77, 53%); stable disease (n = 22, 15%). Second-line therapy: PBC (n = 95, 66%); platinum-free regimen (PFR) (n = 25, 17%); ICI (n = 24, 17%). Median [95% confidence interval] PFS (months): PBC 5.0 [3.8–6.2]; PFR 4.0 [1–7.0]; ICI 2.0 [0.4–3.6] (p = 0.16). For PBC, PFR, and ICI, respectively: OS1 30, 23, and 29 months (p = 1.02); OS2 14, 10, and 16 months (p = 0.25); PR, 26%, 16%, and 21% patients; CR, 0%, 8%, and 4% patients. For subsequent lines, ICIs were administered for PBC (n = 11, 12%) and PFR (n = 2, 8%). No predictive factor for efficacy (PFS, OS) was identified.ConclusionsOur retrospective study suggests similar efficacy regarding OS2 for second-line chemotherapy or ICI in R/M-HNSCC patients with progression ≥ 6 months after the last first-line platinum dose.

Neoadjuvant tislelizumab, a PD-1 mAb plus nab-paclitaxel (nab-P) followed by tislelizumab plus epirubicin/cyclophosphamide (EC) for triple-negative breast cancers (TNBC): Interim analysis of clinical response in a phase 2 TREND trial.

e14623 Background: Chemo-based immunotherapy improves the prognosis of TNBC. However, the dominant population and optimal chemo-backbone of neoadjuvant immunotherapy remain undefined. Aim of TREND trial was to assess the efficacy and safety of tislelizumab in combination with nab-P and EC (nab-P-EC) in neoadjuvant therapy of TNBC. Methods: In this prospective, single-arm phase 2 clinical study, untreated TNBC patients who have clinically node-positive or at least T2 disease without distant metastasis were eligible. Before surgery, enrolled patients received tislelizumab (200 mg IV Q3W) plus weekly nab-P (100 mg/m² IV Q3W) for 12 weeks, followed by tislelizumab (200 mg IV Q3W) plus epirubicin (75 mg/m² IV Q3W) and cyclophosphamide (600 mg/m² IV Q3W) for the subsequently 12 weeks. The primary endpoint was pCR (ypT0/Tis ypN0) and secondary endpoints was objective response rate (ORR, RECIST v1.1). Combined positive score (CPS) of PD-L1 expression in pre-treatment biopsy samples was tested by PD-L1 IHC 22C3 PharmDx. Single-cell RNA sequencing, single-cell TCR sequencing, mass cytometry by time of flight, whole exome sequencing, RNA-seq and olink-assay were performed on pre- and post-treatment samples from primary tumors, metastatic lymph nodes and peripheral blood. Results: Of 43 enrolled patients from Nov 2020 to Nov 2022, 21 patients completed neoadjuvant therapy and accepted surgery in per protocol set (PPS; median age 48 years; range 25-69 years), and 16 were still on treatment. In PPS, the pCR (ypT0/is ypN0) rate was 71.43% (15/21). For different target lesions, 15 patients achieved ypT0/Tis (pCR rate = 71.43%) and 20 reached ypN0 (pCR rate = 95.24%). When stratified by CPS, pCR (ypT0/is ypN0) rate were 68.4%,72.2% and 76.9% in CPS ≥ 1, CPS ≥ 5 and CPS ≥ 10 subgroups, respectively. The ORR in PPS was 90.48% (n = 19/21, 95% CI: 68.18 - 98.33) and DCR reached 95.24% (n = 20/21, 95% CI: 74.13 - 99.75), including 9 complete response and 10 partial response. Treatment emergent adverse event (TEAE) occurred in 74.4% patients (32/43), of which 69.8% were Immune-related adverse event (irAE) (30/43). Grade ≥ 3 IrAE was 7.0% (3/43) and no treatment-related deaths were found. Conclusions: Combining tislelizumab and neoadjuvant nab-P-EC achieved favorable efficacy in TNBC, supporting that platinum-free regimen was non-inferior as a chemo-backbone. For heterogeneity of efficacy to immunotherapy, metastatic tumors in lymph nodes responded better to tislelizumab than primary tumor, suggesting that node-positive patients were potentially dominant population of neoadjuvant immunotherapy. Further results from the ongoing TREND trial and subsequent analysis of mechanism are urgently awaited. Clinical trial information: ChiCTR2000035262 .

Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer.

The choice of chemotherapeutic regimen for triple-negative breast cancer (TNBC) remains controversial. Homologous recombination deficiency (HRD) has attracted increasing attention in informing chemotherapy treatment. This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy. Chinese patients with TNBC who received chemotherapy between May 1, 2008 and March 31, 2020 were retrospectively analyzed with a customized 3D-HRD panel. HRD positivity was defined by an HRD score ≥ 30 or deleterious BRCA1/2 mutation. A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort (NCT01150513) and a metastatic cohort, and 189 patients with available clinical and tumor sequencing data were included. In the entire cohort, 49.2% (93/189) of patients were identified as HRD positive (40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of ≥ 30). In the first-line metastatic setting, platinum therapy was associated with longer median progression-free survival (mPFS) than platinum-free therapy [9.1 vs. 3.0 months; hazard ratio (HR), 0.43; 95% confidence interval 0.22-0.84; P = 0.01]. Among HRD-positive patients, the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy (13.6 vs. 2.0 months; HR, 0.11; P = 0.001). Among patients administered a platinum-free regimen, HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients (P = 0.02; treatment-biomarker P-interaction = 0.001). Similar results were observed in the BRCA1/2-intact subset. In the adjuvant setting, HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy (P = 0.05, P-interaction = 0.02). HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.

Treatment of Recurrent Epithelial Ovarian Cancer.

Epithelial ovarian cancer is the most common cause of death from gynecological tumors. Most patients with advanced ovarian cancer develop recurrence after concluding first-line therapy, making further lines of therapy necessary. The choice of therapy depends on various criteria such as tumor biology, the patientʼs general condition (ECOG), toxicity, previous chemotherapy, and response to chemotherapy. The platinum-free or treatment-free interval determines the potential response to repeat platinum-based therapy. If patients have late recurrence, i.e. > 6 months after the end of the last platinum-based therapy (i.e., they were previously platinum-sensitive), then they are usually considered suitable for another round of a platinum-based combination therapy. Patients who are not considered suitable for platinum-based chemotherapy are treated with a platinum-free regimen such as weekly paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine, or topotecan. Treatment for the patient subgroup which is considered suitable for platinum-based therapy but cannot receive carboplatin due to uncontrollable hypersensitivity reactions may consist of trabectedin and PLD. While the use of surgery to treat recurrence has long been a controversial issue, new findings from the DESKTOP III study of the AGO working group have drawn attention to this issue again, particularly for patients with a platinum-free interval of > 6 months and a positive AGO score. Clinical studies have also shown the efficacy of angiogenesis inhibitors such as bevacizumab and the PARP inhibitors olaparib, niraparib and rucaparib. These drugs have substantially changed current treatment practice and expanded the range of available therapies. It is important to differentiate between purely maintenance therapy after completing CTX, continuous maintenance therapy during CTX, and the therapeutic use of these substances. The PARP inhibitors niraparib, olaparib and rucaparib have already been approved for use by the FDA and the EMA. The presence of a BRCA mutation is a predictive factor for a better response to PARP inhibitors.

Clinical outcomes of platinum-based chemotherapy plus cetuximab for recurrent or metastatic squamous cell carcinoma of the head and neck: comparison between platinum-sensitive and platinum-resistant patients

Background: Combination therapy consisting of a platinum agent, 5-fluorouracil and cetuximab (EXTREME regimen) is recommended for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). However, it is advisable to use platinum-free regimens as first-line therapy in patients resistant to platinum agents. There has been no report comparing EXTREME regimen outcomes between platinum-resistant and platinum-sensitive patients.Objectives: We conducted this study to examine the outcomes of the EXTREME regimen as first-line therapy in patients with R/M-SCCHN and a history of platinum agent use and assess whether the EXTREME regimen outcomes differ between platinum-resistant and platinum-sensitive patients.Materials and methods: The study included 32 patients with R/M-SCCHN who received the EXTREME regimen as first-line therapy. Patients with recurrence or metastasis within 6 months after cisplatin administration were considered platinum-resistant and those with no recurrence or metastasis within 6 months were considered platinum-sensitive.Results: 17 patients were platinum-resistant and 15 patients were platinum-sensitive. The median survival durations were 10.6 and 19.9 months in the platinum-resistant and platinum-sensitive patients, respectively, and the prognosis was significantly better in the platinum-sensitive patients (p = .02).Conclusions: Our findings suggest that the EXTREME regimen is useful as first-line therapy for R/M-SCCHN in platinum-sensitive patients.

Phase II Study of Irinotecan plus S-1 Combination for Previously Untreated Advanced Non-Small Cell Lung Cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0601

Objective: Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC. Methods: Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m², days 1 and 15) and oral S-1 (80 mg/m², days 1–14). The primary endpoint was response rate, while secondary endpoints were overall survival, progression-free survival (PFS), and safety. Results: A total of 112 cycles was administered to 40 patients (median 3 cycles; range 1–6 cycles). Twelve patients showed partial response and 17 patients had stable disease, representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common nonhematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055). Conclusion: The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC.

Management of advanced bladder cancer in patients with impaired renal function

Advanced transitional-cell carcinoma of the bladder is the most common cancer of the urinary tract, with a high mortality rate. Cisplatin-based chemotherapy has demonstrated prolonged survival of these patients and is considered the standard of care. Nevertheless, 40–50% of patients have impaired renal function that precludes the use of cisplatin. The non-nephrotoxic platinum analogue, carboplatin, has emerged as the most popular alternative in this setting, used mainly in doublets. However, it has not shown similar efficacy to cisplatin. In this article, platinum-based or platinum-free regimens, monotherapies or combination therapies are discussed as treatment options for this population. Their efficacy and toxicity are also being analyzed. The study of newer targeted therapies in the treatment of bladder cancer is also discussed, as are future perspectives and a five-year view in the treatment of the disease in patients with renal impairment.

A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic Non-Small Cell Lung Cancer

BackgroundTo compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC).MethodsPatients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m2; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m2 on days 1 and 15).ResultsResponse rate was similar between the two arms (DC vs D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC arm and 34.5 months for D arm, progression free survival (PFS) was significantly higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while no significant difference was observed in terms of overall survival (OS) (DC vs D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed.ConclusionsThis study has not achieved its primary objective of significant OS prolongation with docetaxel/carboplatin combination over single-agent docetaxel in patients who had not received front-line docetaxel; however, the docetaxel/carboplatin combination was associated with a significant clinical benefit in terms of PFS.

Phase II study of irinotecan plus S-1 combination for previously untreated advanced non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group 0601

e19012 Background: Platinum-containing therapy is a standard first-line treatment for advanced non-small cell lung cancer (NSCLC). Platinum-free regimens can be alternative if they can provide similar efficacy with better tolerability. This study evaluated the efficacy and safety for combination of irinotecan and S-1, a newly developed oral 5-fluorouracil derivative, for chemotherapy-naïve advanced NSCLC. Methods: In this multicenter phase II trial, we initially planned to enroll 40 patients. Chemotherapy consisted of 4-week cycles of irinotecan (100 mg/m2 IV, day 1 and 15) and S-1 (80 mg/m2 orally, day 1–14). Primary end point was response rate; secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. Association of UGT1A1 genotypes (*6 and *28) with frequency of severe toxicity was also examined. Results: A total of 112 cycles was administered into 40 patients (median, 3 cycles: range, 1–6). Median age was 64 years (range, 42–75); 29 patients (73%) had adenocarcinoma, and 8 patients (20%) had squamous cell carcinoma. Majority of the patients (32 cases, 80%) had stage IV disease. Twelve patients exhibited partial response (PR), and 17 patients exhibited stable disease (SD), resulting in response rate of 30% [95% confidence interval (95% CI), 16.6–46.5] and disease control rate of 72.5% (95% CI, 56.1–85.4). Median OS and PFS were 13.8 months (95% CI, 10.7–16.9) and 4.7 months (95% CI, 3.4–6.0), respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common non-hematologic toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). There were no treatment-related deaths. Among the 40 patients, there were 1 homozygous and 8 heterozygous for UGT1A1*6, whereas 7 heterozygous for UGT1A1*28; none of the patients had both genotypes. Patients with homozygous or heterozygous for UGT1A1*6 showed a trend for high incidence of grade 3 diarrhea (p = 0.055). No association of UGT1A1*28 with severe toxicity was observed in this study. Conclusions: Irinotecan and S-1 combination is an alternative treatment with tolerable toxicity for previously untreated advanced NSCLC. No significant financial relationships to disclose.

A phase I trial of docetaxel and vinorelbine in patients with advanced non-small cell lung cancer

Advanced non-small cell lung cancer (NSCLC) remains a difficult cancer to treat, and evolution of platinum-free regimens in a first-line setting is ongoing. This was a dose-finding study on the docetaxel and vinorelbine combination. Docetaxel was given at 60 mg/m(2) on day 1 only, and vinorelbine was given on days 1 and 15 starting at 20 mg/m(2), then escalated to 30 and 40 mg/m(2) in two dose cohorts. Each cycle lasted 28 days. The maximum tolerated dose was 60 mg/m(2) docetaxel and 30 mg/m(2) vinorelbine. Twenty-one patients were enrolled and showed an overall response rate of 9.5%, with stable disease documented in 33% of patients. The dosage schedule of this combination resulted in acceptable toxicities. The median time to progression was 5.86 months (95% CI 2.50-9.22), and median survival was 10.96 months (95% CI 1.42-20.51) with a 1-year survival rate of 50%. This combination may be important for patients with NSCLC.

Topotecan and etoposide as first-line therapy for extensive disease small cell lung cancer: a phase II trial of a platinum-free regimen

In the treatment of extensive disease of small cell lung cancer (ED SCLC) there is an urgent need for more effective and better-tolerated drug regimens. We report on a prospective phase II trial performed to evaluate the efficacy and safety of a platinum-free regimen--containing topotecan and etoposide--in the first-line treatment of ED SCLC. Between December 1999 and July 2001, 28 chemotherapy-naive patients with ED SCLC were recruited; 9 patients had stage IIIB disease and 19 patients had stage IV disease. Based on phase I results, patients received treatment with intravenous topotecan 1 mg/m2 (days 1-5) followed by intravenous etoposide 75 mg/m2 (days 8-10). Treatment courses were repeated every 28 days for a maximum of 6 cycles. A confirmed response rate of 46.4% with 1 complete response (CR) and 12 partial responses (PR) (95% CI=27.5-66.1%) was observed. Stable disease (SD) was observed in 18% of patients. The median time to response was 7.9 weeks (range: 7.7-15.1 weeks) and median survival was 29.9 weeks (range from 3.3 to 91.4 weeks). Main toxicities encountered were haematological with Grade III/IV neutropenia in 2.6/1.5% of courses and Grade III/IV thrombocytopenia in 1.8%/0.7% of courses. These toxicities were manageable and were not associated with clinical sequels. Non-haematological toxicities were generally mild with no Grade III/IV toxicities reported apart from Grade III alopecia. The combination therapy of topotecan and etoposide is active in first-line chemotherapy for patients with ED SCLC. The regimen showed a tolerable safety profile. Since drug scheduling plays a critical role in the combination of topoisomerase I and II inhibitors, concurrent administration of topotecan and etoposide might increase the efficacy.

Ifosfamide, vinorelbine and gemcitabine in advanced non-small cell lung cancer. A phase I study

The objective of this phase I study was to identify the maximum tolerated dose (MTD) and toxicity of a three drug, platinum-free regimen, including gemcitabine, ifosfamide and vinorelbine, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). 33 chemotherapy-naı̈ve patients with histologically confirmed, unresectable NSCLC, received fixed doses of ifosfamide (1500 mg/m 2 days 1–3 with mesna) and vinorelbine (25 mg/m 2 days 3 and 8). The gemcitabine dose was escalated from 500 to 1200 mg/m 2 on days 3 and 8 every third week. The escalation was stopped at dose level 4 (gemcitabine 1200 mg/m 2) since all 3 patients of this cohort showed dose-limiting thrombocytopenia and/or neutropenia at treatment cycle 1. The dose recommended for phase II trials is: gemcitabine 1000 mg/m 2 and vinorelbine 25 mg/m 2 given on days 3 and 8 plus ifosfamide 1500 mg/m 2 on days 1–3. An encouraging response rate of 50% (95% confidence interval (CI): 32–68%) was observed in 32 patients evaluated. Our results show that ifosfamide, vinorelbine and gemcitabine can be safely administered as outpatient chemotherapy for NSCLC. Myelosuppression is the dose-limiting toxicity (DLT) of this regimen with no major subjective side-effects observed.

Ten-year results of a randomised trial comparing cisplatin with cisplatin and cyclophosphamide in advanced, suboptimally debulked ovarian cancer

176 eligible patients with advanced suboptimally operated ovarian carcinoma were randomly allocated to receive either cisplatin 75 mg/m 2 or cisplatin 50 mg/m 2 and cyclophosphamide 500 mg/m 2 (CP) every 28 days for six courses. The overall clinical response rates (complete response plus partial response) were 52 and 63% for CP and cisplatin, respectively (non-significant). Including results obtained by second-look laparotomy, we did not observe a statistically significant difference in response rates in the two treatment groups. Median progression-free survival was 10 and 11.9 months for CP and cisplatin, respectively (non-significant). No significant difference was observed in overall survival, with a median of 19.4 and 21.5 months for CP and cisplatin, respectively. Thirty-seven platinum-resistant and 27 platinum-sensitive tumours were treated with carboplatin or cisplatin as second-line therapy. Response rates to platinum second-line therapy were 6 and 50% for resistant and sensitive tumours, respectively ( P<0.001). This difference in response rate was also confirmed by survival analysis. Patients with platinum-sensitive tumours survived longer when they were treated with platinum-containing chemotherapy ( P=0.005). Median survival was 22.8 and 8.5 months after initiation of second-line treatment for the platinum-containing and platinum-free regimens, respectively. In summary, we observed in suboptimally operated ovarian carcinoma patients similar response rates, progression-free interval, and overall survival for equitoxic cisplatin and CP. However, the doses of cisplatin and cyclophosphamide chosen were substantially lower than current standard doses of CP. Our study demonstrates, therefore, that a suboptimal dose of CP is as effective as optimal dose monotherapy cisplatin. Patients with recurrences considered as platinum-sensitive had a significantly higher response rate and improved survival when retreated with platinum-containing therapy.