Cisplatin For First-line Treatment Research Articles

PD-1 inhibitors combined with paclitaxel and cisplatin in first-line treatment of esophageal squamous cell carcinoma (ESCC): a network meta-analysis

BackgroundThe combinations of PD-1 inhibitors with paclitaxel/cisplatinum (PD-1 + TP) and fluoropyrimidine/cisplatinum (PD-1 + FP) both have been shown to improve overall survival (OS) and progression-free survival (PFS) in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no consensus on which chemotherapy regimen combined with PD-1 has better efficacy. To deal with this important issue in the first-line treatment of patients with ESCC, a network meta-analysis (NMA) was performed.MethodsData were collected from eligible studies searched in Medline, Web of Science, PubMed, the Cochrane Library and Embase. The pooled hazard ratio (HR) for the OS, and PFS, odds ratio (OR) for the objective response rate (ORR) and ≥ 3 grade treatment-related adverse events (≥ 3TRAEs) were estimated to evaluate the efficacy of PD-1 inhibitors combined with TP or FP.ResultsFive RCTs and one retrospective study involving 3685 patients and evaluating four treatments were included in this NMA. Compared to other treatments, PD-1 + TP was better. For the PFS, the HRs for PD-1 + TP compared to PD-1 + FP, TP and FP were 0.59 (0.44, 0.80), 0.56 (0.51, 0.61) and 0.45 (0.37, 0.56) respectively. For the OS, PD-1 + TP was also a better treatment compared to other treatments. The HRs were 0.74 (0.56, 0.96), 0.64 (0.57, 0.71), 0.53 (0.43, 0.67) respectively. For the ORR, there was no significant difference between PD-1 + TP and PD-1 + FP, and the ORs were 1.2 (0.69, 2.11). Compare with TP and FP, PD-1 + TP had an obvious advantage, ORs were 2.5 (2.04, 3.04) and 2.95 (1.91, 4.63). For ≥ 3TRAEs, PD-1 + TP compared to other treatments, ORs were 1.34 (0.74, 2.46) and 1.13 (0.92, 1.38) and 2.23 (1.35, 3.69).ConclusionPD-1 + TP significantly improved both PFS and OS compared to PD-1 + FP. Taking into account both efficacy and safety, PD-1 + TP may be a superior first-line treatment option for ESCC.

95P A single-arm, multicenter phase II trial evaluating TQB2450 plus anlotinib combined with paclitaxel and cisplatin in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC)

95P A single-arm, multicenter phase II trial evaluating TQB2450 plus anlotinib combined with paclitaxel and cisplatin in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC)

Phase III study of NUC-1031 + cisplatin versus gemcitabine + cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121).

TPS4164 Background: Biliary tract cancer (BTC) is an aggressive disease with a poor prognosis. Gemcitabine + cisplatin (GemCis) is the accepted global standard of care (SoC), however key cancer resistance mechanisms associated with the transport, activation and breakdown of gemcitabine are known to limit its clinical activity across a range of tumor types, including BTC. NUC-1031 is a phosphoramidate transformation of gemcitabine designed to overcome these key resistance mechanisms and generate much higher levels of the active anti-cancer metabolite, dFdCTP, in cells. Promising efficacy has been observed with single-agent NUC-1031 in a phase I study in advanced solid tumors and in the phase Ib ABC-08 study of NUC-1031 + cisplatin for first-line treatment of advanced BTC. Of 21 patients enrolled in 2 dose cohorts (NUC-1031 625 mg/m2 or 725 mg/m2 + cisplatin 25 mg/m2 on Days 1 and 8 of 21-day cycle), 16 were considered to be efficacy evaluable. In this population, 1 patient had a CR and 6 patients had PRs, resulting in an ORR of 44% (7/16). This compares favorably to the 26% ORR reported for the SoC regimen. In addition, 6 patients had SD, resulting in a DCR of 81% (13/16). The combination was well tolerated with no unexpected AEs or DLTs. The recommended dose of NUC-1031 with cisplatin was 725 mg/m2. The tolerability profile, together with encouraging efficacy led to initiation of a global registrational study. Methods: NuTide:121 is a phase III, open-label, randomized study of NUC-1031 + cisplatin vs GemCis for first-line treatment of advanced BTC. Patients ≥18 years with histologically- or cytologically-confirmed BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), who have had no prior systemic chemotherapy for locally advanced/metastatic disease, are eligible. A total of 828 patients are being randomized (1:1) to either 725 mg/m2 NUC-1031 or 1000 mg/m2 gemcitabine, both with 25 mg/m2 cisplatin, administered on Days 1 and 8 of 21-day cycles. Primary endpoints are OS and ORR. Secondary endpoints include PFS, safety, PK and patient-reported quality of life. In addition to the final analysis, three interim analyses are planned. The study has passed an initial safety analysis, with no protocol changes required. NuTide:121 is being conducted at approximately 130 sites across North America, Europe and Asia Pacific. Clinical trial information: NCT04163900.

NUC-1031 in combination with cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121).

TPS602 Background: Biliary tract cancer (BTC) carries a poor prognosis and has no approved treatments. Although gemcitabine + cisplatin (GemCis) is accepted as the global standard of care (SoC) for 1st-line treatment, the reported unconfirmed ORR and OS from randomized studies of this combination are low at 18.5-26.1% and 11.2-11.7 months, respectively. NUC-1031, a phosphoramidate transformation of gemcitabine, is designed to overcome key cancer resistance mechanisms associated with gemcitabine. Promising signs of efficacy have been observed with single-agent NUC-1031 in a Phase I study in advanced solid tumors (Blagden et al 2018) and in the Phase Ib ABC-08 study of NUC-1031 + cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for the 1st-line treatment of advanced BTC. Of 14 patients (pts) enrolled in 2 cohorts (NUC-1031: 625 mg/m2 and 725 mg/m2), 1 pt achieved a CR and 6 pts achieved PR, giving an unconfirmed ORR of 50% and representing an approximate doubling of ORR over SoC. The combination was well-tolerated with no unexpected adverse events or dose-limiting toxicities. The RP2D of NUC-1031 in combination with cisplatin is 725 mg/m2. The tolerability profile together with robust efficacy signals suggested NUC-1031 + cisplatin may represent a more effective therapy than GemCis for BTC and led to initiation of a global Phase III study. Methods: A Phase III, open-label, randomized head-to-head study of NUC-1031 + cisplatin versus GemCis for 1st-line treatment of advanced BTC will include pts ≥18 years with histologically- or cytologically-proven BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), who have had no prior systemic chemotherapy for locally advanced/metastatic disease. A total of 828 pts will be randomized (1:1) to either 725 mg/m2 NUC-1031 + 25 mg/m2 cisplatin or 1000 mg/m2 gemcitabine + 25 mg/m2 cisplatin, administered on days 1 and 8 of a 21-day cycle. Primary objectives are OS and ORR. Secondary objectives include further measurements of efficacy, safety, pharmacokinetics, and patient-reported quality of life. The study will be conducted at approximately 120 sites across North America, Europe and Asia Pacific countries. Clinical trial information: NCT04163900.

NUC-1031 in combination with cisplatin for first-line treatment of advanced biliary tract cancer.

TPS4156 Background: Cisplatin and gemcitabine (CisGem) is the global standard of care for 1st-line treatment of patients (pts) with advanced biliary tract cancer (BTC). No agents have regulatory approval for this disease. CisGem achieves an objective response rate (ORR) of 26% and median overall survival (OS) of 11.7 months (ABC-02). Key cancer resistance mechanisms limit gemcitabine efficacy. NUC-1031, a phosphoramidate transformation of gemcitabine, is designed to overcome resistance mechanisms associated with poor gemcitabine response. Promising signs of efficacy have been observed with single agent in a phase I study in solid tumors (Blagden et al 2018) and in the phase Ib ABC-08 study of NUC-1031 + cisplatin 25 mg /m2 d1, d8 q 21 days for the 1st-line treatment of advanced BTC. 14 pts have been enrolled across 2 cohorts (NUC-1031: 625 mg/m2 and 725 mg/m2). In 11 pts evaluable for response ORR was 64% (1 CR, 6 PRs) and DCR was 73%. PFS/OS data is maturing. The combination was very well-tolerated with no unexpected adverse events or dose-limiting toxicities. The RP2D in combination with cisplatin is 725 mg/ m2. Safety, coupled with encouraging efficacy signal has led to initiation of a global Phase III development program. Methods: A Phase III, open-label, randomized head-to-head study of NUC-1031 + cisplatin versus CisGem for the 1st-line treatment of advanced BTC will include pts ≥18 years with histologically- or cytologically-proven BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), that is not resectable and who have had no prior systemic chemotherapy for locally advanced/metastatic disease. A total of 828 pts will be randomized (1:1) to either 725 mg/m2 NUC-1031 + 25 mg/m2 cisplatin or 1000 mg/m2 gemcitabine + 25 mg/m2 cisplatin, administered on Days 1 and 8 of a 21-day cycle, respectively. Primary objectives are OS and ORR. Secondary objectives include further measurements of efficacy, safety, pharmacokinetics, and patient-reported quality of life. The study will be conducted at approximately 120 sites across North America, Europe and Asia Pacific countries. Clinical trial information: NCT02351765.

SC23.04 Cooperative Groups in China: The CSCO Experience

SC23.04 Cooperative Groups in China: The CSCO Experience

Efficacy and prognostic factors of 178 advanced non-small lung cancer patients undergoing different second-line chemotherapeutic regimens

The purpose of this study is to explore the efficacy and predictors of second-line chemotherpy in advanced non-small cell lung cancer patients and suggest optimal protocols suitable for differently characterized patients. The clinical data of 178 advanced NSCLC patients second-line-treated in Tianjin Cancer Hospital from 2009.1.1 to 2013.12.31 were retrospectively analyzed. According to the different second-line treatments, the patients were divided into standard mono-drug therapy group (46 cases), endostar combined with standard mono-drug therapy group (42 cases), and platinum-based doublet chemotherapy group (90 cases). Kaplan-Meier and Log-rank analyses were used to estimate and compare the survival rates in the groups, and Cox's hazard regression model was used to determine the prognostic factors. Chi-square test was used to analyze the differences among different groups. The median progression-free survivals (mPFS) were 50 days, 54 days, and 79 days (P=0.042) for the standard mono-drug therapy group, endostar combined with standard mono-drug therapy group, and platinum-based doublet chemotherapy group, respectively. The differences between the mono-drug therapy group and doublet chemotherapy group were statistically significant (P=0.011). The disease control rate (DCR) for each group was 26.1%, 47.6% and 46.7% (P=0.041), and the DCR were statistically significantly different between the mono-drug therapy group and doublet chemotherapy group (P=0.016), and between the mono-drug therapy group and endostar combined with standard mono-drug therapy group (P=0.041). The overall response rate (ORR) for each group was 2.2%, 0, and 4.4% (P>0.05 for all). Multivariate analysis showed that the period from the begining of first-line to second-line chemotherapy (progression-free time), base-line clinical stage, neuron specific enolase (NSE) before second-line therapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS (P<0.005 for all). Subgroup analysis indicated that the patients obtained more clinical benefit from doublet chemotherapy rather than mono-drug therapy, with following factors: age<60 years, paclitaxel plus cisplatin for first-line treatment, chemotherapy cycles ≤4, CR, PR and SD for response, progression time within 3-6 months from the begining of first-line to second-line chemotherapy, performance status score≤1 at the begining of second-line therapy, Ⅳ stage, and mild leukopenia (P<0.05 for all). The patients whose progression-free survival time within 3-6 months from the begining of the first-line to second-line chemotherapy got more clinical benefit from endostar combined with standard mono-drug chemotherapy than mono-drug therapy (P=0.006). The period from the begining of first-line to second-line chemotherapy, base-line TNM stage, NSE before second-line chemotherapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS. Platinum-based doublet chemotherapy and endostar plus standard second-line regimen can improve the efficacy in some characterized advanced NSCLC as compared with the patients by standard mono-drug therapy, wherein the platinum-based chemotherapy revealed the best efficacy.

Pembrolizumab (MK-3475) plus 5-fluorouracil (5-FU) and cisplatin for first-line treatment of advanced gastric cancer: Preliminary safety data from KEYNOTE-059.

161 Background: Standard first-line treatment for advanced gastric cancer includes combination chemotherapy with a platinum agent and a fluoropyrimidine. The anti–PD-1 humanized monoclonal antibody pembrolizumab (pembro) has shown promising antitumor activity as monotherapy in patients (pts) with advanced gastric cancer. We report preliminary safety data for pts with advanced gastric cancer treated with pembro + cisplatin and 5-FU in the multicohort, phase 2 KEYNOTE-059 study (NCT02335411). Methods: Eligible pts were aged ≥ 18 y and had HER2– relapsed or metastatic gastric or gastroesophageal junction adenocarcinoma, ECOG PS 0-1, and no prior therapy for metastatic disease. Pts received pembro 200 mg + 5-FU 800 mg/m2 (or capecitabine 1000 mg/m2 in Japan) + cisplatin 80 mg/m2 Q3W for 6 cycles followed by pembro + 5-FU for up to 2 y or until confirmed progression, intolerable toxicity, or investigator decision. Primary end point was safety and tolerability of the combination. Results: Of the 17 pts enrolled (10 from Asia, 7 from outside Asia), 70.6% were men, and median age was 58.0 y. Three pts (17.6%) had a prior gastrectomy—2 total, 1 partial. As of the Aug 12, 2015, data cutoff date, median follow-up duration was 3.6 mo (range 2.6-5.4), and pts received a median of 5 treatment cycles (range 3-7). Only 1 pt (5.9%) discontinued treatment (due to progressive disease). There were no treatment-related deaths or discontinuations. Twelve pts (70.6%) experienced treatment-related adverse events (AEs) of any grade, most commonly neutropenia/decreased neutrophils (n = 7, 41.2%), stomatitis (n = 6, 35.3%), and decreased appetite (n = 5, 29.4%). Eight pts (47.1%) experienced ≥ 1 grade 3-4 treatment-related AE; only neutropenia/decreased neutrophils (n = 4 [23.5%] grade 3, n = 3 [17.6%] grade 4) occurred in &gt; 1 pt. AEs of interest based on immune etiology, regardless of attribution by investigator, were grade 2 infusion-related reaction and grade 2 pruritus (n = 1 [5.9%] each). Conclusions: Preliminary data from KEYNOTE-059 suggest the combination of pembro, cisplatin, and 5-FU has a manageable safety profile as first-line therapy in pts with advanced gastric cancer. Clinical trial information: NCT02335411.

Docetaxel and Cisplatin in First Line Treatment of Patients with Unknown Primary Cancer: A Multicenter Study of the Anatolian Society of Medical Oncology

The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel (75 mg/m2, day 1) and cisplatin (75 mg/m2, day 1) was performed as a first line regimen every 21 days. The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP.

Comparison of Cisplatin-5-Fluorouracil-Folinic Acid versus Modified Docetaxel-Cisplatin-5-Fluorouracil Regimens in the First-Line Treatment of Metastatic Gastric Cancer

Objective: Prognosis of metastatic gastric cancer is poor and median survival is between 3 and 5 months. Response rates of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in first-line treatment have been found to be 20–25% in the English literature. It has been demonstrated that adding docetaxel to combination chemotherapy improved time to progression and overall survival. However, the toxicity rates of the docetaxel-cisplatin-5-FU protocol were high. In our study we compared efficacy and toxicity of cisplatin-5-FU-folinic acid (CFF) and modified docetaxel-cisplatin-5-FU (mDCF) regimens in the first-line treatment of metastatic gastric cancer. Patients and Methods: Between June 2004 and October 2008, 70 patients with previously untreated metastatic gastric cancer treated with CFF (n = 30) and mDCF (n = 40) were retrospectively evaluated in the study. Survival and toxicity data were compared. Results: Median age of the patients was 53 years (range 23–69). Forty-eight percent of the patients were male and 75.7% had an ECOG performance status of 0–1. Prognostic factors including age, ECOG performance status, histopathological grade, and number and sites of metastases were similar between the groups. Objective response rates (complete and partial response) were higher in the mDCF group (30.0 vs. 13.3%, p = 0.19). While toxicity was acceptable in both groups, the most common grade 3–4 toxicities were anemia in 3.3 and 5.0%, neutropenia in 20 and 7.5%, febrile neutropenia in 6.7 and 5.0%, and diarrhea in 3.3 and 5.0% in the CFF and mDCF groups, respectively. Median follow-up was 10.3 (1.5–59.6) months. During that period 90 and 97.5% of the patients were dead in the CFF and mDCF groups, respectively. Median time to progression was 4.4 (95% CI 1.8–7.0) and 6.2 months (95% CI 5.6–6.8) (p = 0.85), median overall survival was 6.5 (95% CI 1.8–11.2) and 8.7 months (95% CI 6.7–10.7) (p = 0.88) in the CFF and mDCF groups, respectively. Conclusion: The mDCF regimen has been found to be more favorable than the CFF regimen with an acceptable toxicity profile in the first-line treatment of metastatic gastric cancer.

The Role of Pemetrexed in the Pharmacotherapy of Malignant Pleural Mesothelioma

Among newer cytotoxic agents, pemetrexed gained much interest because of its particular mechanism of action. In fact, pemetrexed is a multi-target agent able to inhibit at least three crucial enzymes involved in the folate pathway: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. The ability to inhibit multiple enzymes, confers to this drug a clinical advantage by increasing the spectrum of tumors with biochemical profiles potentially sensitive to the drug. Due to the good toxicity profile of pemetrexed, the combination with cisplatin resulted feasible and effective. Pemetrexed is currently approved in combination with cisplatin for first line treatment in patients with unresectable malignant pleural mesothelioma. Pemetrexed is the first agent approved for the treatment of malignant pleural mesothelioma. Generally, pemetrexed is considered a well tolerated drug and the addition of folic acid, vitamin B12, and dexamethasone markedly reduced the incidence of grade 3 and 4 hematologic and non-hematologic toxicities. Pharmacology, pharmacokinetics, efficacy, safety, and current and potential roles of pemetrexed in therapy for malignant pleural mesothelioma were reviewed.

Analisi di costo-efficacia di pemetrexed più cisplatino versus gemcitabina più cisplatino nel trattamento di prima linea in pazienti con NSCLC non squamoso in stadio avanzato

The aim of this study, conducted from the perspective of the Italian National Health Service, is to assess the cost-effectiveness of pemetrexed plus cisplatin versus gemcitabine plus cisplatin for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Outcome results and resource consumption data were derived from a phase III, randomized study (JMBD-GVS) of 1725 chemotherapy-naive patients with stage IIIB or IV NSCLC. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with non-squamous NSCLC (median survival, 11.8 vs 10.4 months, respectively). Taking into account the cost of therapies, the overall mean treatment cost was lower with cisplatin/gemcitabine regimen (€8,316.47) than with cisplatin/pemetrexed regimen (€12,364.29). Sensitivity analysis proved that the incremental cost-effectiveness for life-years gained (€34,695.59) was below the internationally accepted threshold (€50,000). This economic evaluation showed that cisplatin plus pemetrexed regimen, as first-line therapy for NSCLC, can provide an improvement in survival at reasonable costs if compared to internationally accepted threshold.

Cisplatin- Versus Carboplatin-Based Chemotherapy in First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: An Individual Patient Data Meta-analysis

Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed. Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided. Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy. Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.

A phase II study of oral vinorelbine in combination with cisplatin conducted in Taiwan in patients with unresectable localized or metastatic non-small cell lung carcinoma

Intravenous vinorelbine plus cisplatin is widely prescribed for the treatment of NSCLC. The objective of this phase II study was to define the efficacy of an oral form of vinorelbine combined with cisplatin for first line treatment of advanced/metastatic NSCLC. From September 2002 to December 2003, 46 chemotherapy-naive patients received 80 mg/m(2) of cisplatin on day 1 and oral vinorelbine at 60 mg/m(2) on days 1 and 8, every 3 weeks. After an independent panel review, the response rate was 37.5 % [95% confidence interval (CI): 22.7-54.2%] in the evaluable population and 32.6% [95% CI: 19.5-48] in the intent-to-treat population. Median progression-free survival was 5.6 months and overall survival was 11.2 months. Grades 3 and 4 neutropenia was observed in 58.7% of patients, with febrile neutropenia and neutropenic infection in 4.3 and 8.7% of patients, respectively. The main non-haematological toxicities were hypotension, fatigue (8.7% for each) and gastrointestinal disorders with rare grades 3 and 4. These results suggest that the combination of cisplatin at 80 mg/m(2) on day 1 with oral vinorelbine at 60 mg/m(2) on days 1 and 8, every 3 weeks, is an active regimen, associated with acceptable toxicity. Oral vinorelbine is therefore a good alternative to the i.v. formulation.

Docetaxel and cisplatin as first-line chemotherapy in advanced NSCLC

7343 Background: Untreated cases of advanced lung cancer in India have a median survival of few weeks only (less than 2 months). However, use of various chemotherapeutic agents increases the survival (Behera- Ind J Paed Oncol, 1995). Docetaxel in combination with cisplatin for first-line treatment is a good choice for locally advanced or metastatic NSCLC (Med Clin, Barc 2004). We describe our experience with Docetaxel and Cisplatin in a group of Indian patients with advanced NSCLC. Method: 130 patients of stage IIIB/IV histologically proved Non-small Cell Lung Cancer were included in the study. There were 116 males with their age ranging from 40 to 81 years and 14 females (age range 40–67). The performance status ranged from 60 to 100 (Kornofsky scale). Docetaxel 100mg/m2 and Cisplatin 60 mg/m2 was administered on day 1. The course was repeated every 28 days and the target was to give 5 such courses of chemotherapy. Fourty three patients received additional local radiotherapy of 20 to 50Gy. 84 patients completed 5 cycles of therapy. Result: Complete radiological response was observed in 22 (18.5%) and partial response in 28 (33%). The lesions remained stable ranging from 10 weeks to 41 weeks before they showed progression. At the time of data analysis the median survival has been 44.5+ weeks for those who completed five cycles. 118 patients (91%) are surviving beyond 6 months and 42 patients (32.3%) are alive beyond one year and 14 patients (10.7%) are still alive after 2 years. Thirty two patients gained weight during therapy with the mean increase of 4.1kg and 24 lost weight with a mean of 2.8 kg. Performance status improved in 24 and deteriorated in 9; in the remaining patients it was static. Side effects were minimal (alopecia, nausea, vomiting, diarrhea, skin changes and neuropathy) and not serious. Diarrhoea was observed in 32 (24.6%)of the patients that could be managed with usual antidiarrhoeals. Conclusion: Docetaxel and cisplatin combination as first line chemotherapy in advanced non small cell lung cancer is effective and comparable to other commonly used regimens. Although the regimen is costlier in Indian standards, it is effective with minimal side effects and should be tried in those who could afford it. No significant financial relationships to disclose.

Spotlight on Paclitaxel in Ovarian Cancer*

Paclitaxel belongs to the group of antitumor agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomized phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-hematologic adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer.

Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was US $18,200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11,600 Canadian dollars ($Can) to $Can 24,200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin--a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile--are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.

Phase II study of docetaxel and cisplatin in first line treatment of disseminated small cell lung cancer (SCLC): preliminary results

Phase II study of docetaxel and cisplatin in first line treatment of disseminated small cell lung cancer (SCLC): preliminary results