A randomized phase II trial of cisplatinum plus mitomycin-C plus vinorelbine and carboplatin plus vinorelbine in advanced non-small cell lung cancer

Vinorelbine represents one of the most active agents in advanced non-small cell lung cancer (NSCLC), with response rates of 14-33%. We therefore evaluated the activity and tolerability of two novel vinorelbine-containing regimens in stage IIIB-IV NSCLC. Fifty-two patients were enrolled in a randomized phase II study of cisplatinum (100 mg/m(2)) day 1, mitomycin-C (8 mg/m(2)) day 1, and vinorelbine (25 mg/m(2)) days 1 and 8 (Arm A); and carboplatin (400 mg/m(2)) day 1, in combination with vinorelbine (25 mg/m(2)) days 1 and 8 (Arm B). Cycles were repeated every 3 weeks. All patients were assessable for reponse and side effects. Patients were well balanced between the two Arms in terms of major characteristics. A total of 98 and 91 cycles were delivered respectively in Arm A and Arm B. Eleven objective responses (42%; 95% confidence interval 26-63%) were observed in Arm A and 7 responses (27%; 95% confidence interval 12-48%) in Arm B. Main toxicity was mild or moderate, nausea and vomiting for Arm A and hematological for Arm B. Other side effects included infections and phlebitis and were similar for the two Arms. In conclusion, both schedules demonstrated activity in advanced NSCLC. The three-drug regimen appeared very promising in terms of activity and manageable toxicity.     

Clinical and immunological evaluation of schizophyllan (SPG) in combination with standard chemotherapy in patients with head and neck squamous cell carcinoma

A phase II randomized controlled trial was carried out to evaluate the clinical efficacy and tolerability of Schizophyllan (SPG) used in combination with standard chemotherapy in the neoadjuvant setting in patients with locally advanced head and neck squamous cell carcinoma. Several immunological parameters were considered to assess the immunoregulatory activity of SPG in the: same patients. The clinical and immunological evaluations were performed both before and at the end of the study (4 months later). All patients received standard chemotherapy for head and neck squamous cell carcinoma according to one of the following treatment regimens: 1) cisplatin 100 mg/m(2) i.v, day 1, 5-FU 1,000 mg/m(2) i.v. continuous infusion days 1 to 5; 2) cisplatin 80 mg/m(2) i.v, day 1, 5-FU 600 mg/m(2) i.v. over 4 h days 2 to 5, vinorelbine 20 mg/m(2) i.v. days 2 and 8. Antineoplastic regimens were repeated every 28 days x 4 cycles for approximately 4 months. SPG was administered weekly at a single dose of 40 mg intramuscularly for 4 months in addition to standard chemotherapy. Twenty-six patients were enrolled in the study, 22 of whom were evaluable. Thirteen patients were assigned to Arm A (treatment with SPG associated with chemotherapy, regimen 1 or 2) and 9 patients to Arm B (treatment with chemotherapy, regimen 1 or 2, alone). The overall response rate was not significantly different between the two Arms (92.3% in Arm A vs. 100% in Arm B), although a higher number of complete responses (CR) (3 = 23.1%) was registered in Arm A. Overall, the SPG treatment does not seem to have induced significant changes of the immunological parameters of our patients: this may be due to both the advanced cancer stage and the effect of chemotherapy, which are both well known causes of immunodepression. The significant differences between the two Arms were only: the CD8(+) lymphocytes were decreased in the patients treated with SPG and increased in controls; serum levels of IL-1 alpha was lower in patients treated with SPG than in the control group; the production in culture of IL-1 alpha was higher in Arm A than in Arm B and IL-6 was higher in Arm B than in Arm A. Treatment with SPG was proven safe and was well-toleratedby all patients.     

Prolonged gemcitabine infusion in advanced non-small cell lung carcinoma: a randomized phase II study of two different schedules in combination with cisplatin

BACKGROUND: Preclinical and clinical evidence suggests that a fixed infusion rate of 10 mg/m2 per minute may be more effective than the standard 30-minute infusion of gemcitabine. To investigate the activity and toxicity of the cisplatin plus gemcitabine combination with gemcitabine at a fixed infusion rate in patients with advanced non-small cell lung carcinoma (NSCLC), the authors conducted a randomized Phase II trial of cisplatin plus gemcitabine at the 30-minute standard infusion (calibration arm) or cisplatin plus gemcitabine at a fixed infusion rate (experimental arm). METHODS: A total of 112 chemonaive patients with advanced NSCLC entered the study: 57 patients in Arm A and 55 patients in Arm B. The patients were randomly assigned to receive gemcitabine at a dose of 1000 mg/m2 on Days 1, 8, and 15 over 30 minutes (Arm A) or at a rate of 10 mg/m2 per minute (Arm B). In both treatment arms, cisplatin at a dose of 80 mg/m2 was administered on Day 15 every 28 days. RESULTS: The overall response rates in Arms A and B were 26% (95% confidence interval [95% CI], 10-42%) and 34% (95% CI, 17-52%) (intent-to-treat-analysis), respectively. The median time to disease progression was 6 months (range, 1-26 months) and 8 months (range, 2-21 months), respectively, for Arms A and B and the median overall survival was 13 months (range, 2-26 months) for each arm. It is interesting to note that a high response rate (67%) of brain metastases was noted in the experimental arm. Toxicity was tolerable and comparable in the two arms. CONCLUSIONS: The results of this randomized Phase II trial demonstrated that cisplatin plus gemcitabine with gemcitabine at fixed infusion rate (10 mg/m2 per minute) is active and well tolerated in patients with advanced NSCLC.     

Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer (JCOG9902-DI).

BACKGROUND: The purpose of this study was to evaluate the toxicity and antitumor effect of cisplatin, irinotecan and etoposide combinations on two schedules, arms A and B, for previously untreated extensive small-cell lung cancer (E-SCLC), and to select the right arm for phase III trials. PATIENTS AND METHODS: Sixty patients were randomized to receive either arm A (cisplatin 25 mg/m(2) day 1, weekly for 9 weeks, irinotecan 90 mg/m(2) day 1, on weeks 1, 3, 5, 7 and 9, and etoposide 60 mg/m(2) days 1-3, on weeks 2, 4, 6, 8), or arm B (cisplatin 60 mg/m(2) day 1, irinotecan 60 mg/m(2) days 1, 8, 15, and etoposide 50 mg/m(2) days 1-3, every 4 weeks for four cycles). Prophylactic granulocyte colony-stimulating factor support was provided in both arms. RESULTS: Full cycles were delivered to 73% and 70% of patients in arms A and B, respectively. Incidences of grade 3-4 neutropenia, anemia, thrombocytopenia, infection and diarrhea were 57, 43, 27, 7 and 7%, respectively, in arm A, and 87, 47, 10, 13 and 10%, respectively, in arm B. A treatment-related death developed in one patient in arm A. Complete and partial response rates were 7% and 77%, respectively, in arm A, and 17% and 60%, respectively, in arm B. Median survival time was 8.9 months in arm A, and 12.9 months in arm B. CONCLUSIONS: Arm B showed a promising complete response rate and median survival with acceptable toxicity in patients with E-SCLC, and should be selected for the investigational arm in phase III trials.     

Liposomal cisplatin combined with paclitaxel versus cisplatin and paclitaxel in non-small-cell lung cancer: a randomized phase III multicenter trial

BackgroundLiposomal cisplatin is a new formulation developed to reduce the systemic toxicity of cisplatin while simultaneously improving the targeting of the drug to the primary tumor and to metastases by increasing circulation time in the body fluids and tissues. The primary objectives were to determine nephrotoxicity, gastrointestinal side-effects, peripheral neuropathy and hematological toxicity and secondary objectives were to determine the response rate, time to tumor progression (TTP) and survival.Patients and methodsTwo hundred and thirty-six chemotherapy-naive patients with inoperable non-small-cell lung cancer were randomly allocated to receive either 200 mg/m² of liposomal cisplatin and 135 mg/m² paclitaxel (arm A) or 75 mg/m² cisplatin and 135 mg/m² paclitaxel (arm B), once every 2 weeks on an outpatient basis. Two hundred and twenty-nine patients were assessable for toxicity, response rate and survival. Nine treatment cycles were planned.ResultsArm A patients showed statistically significant lower nephrotoxicity, grade 3 and 4 leucopenia, grade 2 and 3 neuropathy, nausea, vomiting and fatigue. There was no significant difference in median and overall survival and TTP between the two arms; median survival was 9 and 10 months in arms A and B, respectively, and TTP was 6.5 and 6 months in arms A and B, respectively.ConclusionsLiposomal cisplatin in combination with paclitaxel has been shown to be much less toxic than the original cisplatin combined with paclitaxel. Nephrotoxicity in particular was negligible after liposomal cisplatin administration. TTP and survival were similar in both treatment arms.     

Docetaxel versus docetaxel/cisplatin in patients with advanced non-small-cell lung cancer: preliminary analysis of a multicenter, randomized phase III study

The purpose of this study was to compare the efficacy and safety profile of docetaxel versus the combination of docetaxel/cisplatin as frontline treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC) in a multicenter, randomized, prospective phase III trial. Patients with unresectable stage IIIB or metastatic stage IV NSCLC who had previously undergone no chemotherapy were allocated to receive either docetaxel (100 mg/m2 in a 1-hour intravenous infusion; group A) or the combination of docetaxel (100 mg/m2 day 1) and cisplatin (80 mg/m2 day 2) after adequate hydration (group B). Appropriate premedication was given before docetaxel infusion. All patients in group B received granulocyte colony-stimulating factor (150 microg/m2 subcutaneously) support from days 3 to 9 after treatment. Response and toxicity were assessed by World Health Organization criteria. From March 1999 to November 2001, 302 patients were randomly assigned to receive docetaxel (group A, n = 146) or docetaxel/cisplatin (group B, n = 156). The overall response rate was significantly higher in the combination arm (18% vs. 36%; P < 0.001). However, the 2 groups did not differ in median duration of response, time to progression (TTP), median overall survival (OS), or 1-year survival rate. Drug combination was associated with higher toxicity than single-agent therapy. Both regimens had comparable activity in terms of TTP and OS in chemotherapy-naive patients with advanced NSCLC; however, single-agent therapy had a more favorable toxicity profile.     

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.     

Combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support for the treatment of refractory or relapsed small-cell lung cancer

OBJECTIVE: This study was conducted in refractory or relapsed small-cell lung cancer to determine activity and toxicity of the combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support. METHODS: Eighteen patients entered the trial. The median chemotherapy-free interval was 3.1 (range 1.0-14.5) months. Cisplatin (20 mg/m(2)) and ifosfamide (1.5 g/m(2)) were administered on days 1-4, and irinotecan (60 mg/m(2)) was administered on days 1, 8, and 15. In patients who experienced grade 4 hematological toxicity during the prior chemotherapy, the doses of cisplatin and irinotecan were reduced to 15 and 50 mg/m(2), respectively. After 10 patients were entered, cisplatin and irinotecan were administered at doses of 15 and 50 mg/m(2), respectively. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 microgram/m(2) from days 50 to 18, except on the day of irinotecan treatment. RESULTS: All patients could be assessed for response and toxicity. There were 1 complete and 16 partial responses, and an overall response rate of 94.4%. The median survival time of all patients was 339 days, and the 1-year survival rate was 47.5%. Hematological toxicities were significant. Grade 4 neutropenia and thrombocytopenia were observed in 61 and 33% of the patients, respectively. Diarrhea was mild and transient. There was no treatment-related death. CONCLUSION: The combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support was highly active for the treatment of refractory or relapsed small-cell lung cancer.     

Randomised phase II study comparing topotecan/carboplatin administration for 5 versus 3 days in the treatment of extensive-stage small-cell lung cancer.

BACKGROUND: Topotecan is an active drug in small-cell lung cancer (SCLC). In our previous study, a combination of topotecan with cisplatin was associated with a median overall survival of 7.6 or 8.7 months, depending on the duration of treatment. We have replaced cisplatin by carboplatin in this trial, with the objective of creating a more convenient schedule for our patients. Furthermore, we have also compared the standard 5-day schedule with an experimental 3-day schedule. PATIENTS AND METHODS: A total of 100 patients with metastatic disease were included. Patients were randomly assigned to receive either topotecan 0.75 mg/m2, days 1-5, and carboplatin AUC 5, day 5 (arm A) or topotecan 1.25 mg/m2, days 1-3, and carboplatin AUC 5, day 3 (arm B). Six cycles were given at a 3-week interval. RESULTS: A total of 91 patients were assessable for response. The response during therapy was 86.9% in arm A and 80.0% in arm B. Median survival in arm A was 11.8 months and in arm B 11.6 months (P=0.37). CONCLUSIONS: The combination of topotecan and carboplatin is active in extensive-disease SCLC. Toxicity and median survival were comparable in both arms. Three days of treatment seems to be similar to the 5-day regimen.     

Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer

High-dose epirubicin plus cisplatin was compared with the reference regimen of etoposide/cisplatin in small-cell lung cancer (SCLC). Four hundred two previously untreated patients with SCLC were randomized to receive etoposide 100 mg/m(2) on days 1-3 and cisplatin 100 mg/m(2) on day 1 or epirubicin 100 mg/m(2) and cisplatin 100 mg/m(2) on day 1 every 21 days for a total of 6 cycles. Patients were stratified according to treatment center and extent of disease (limited disease, n = 207; extensive disease, n = 195). Patients with limited disease were treated with thoracic radiation therapy after completion of chemotherapy, and those who exhibited a complete response were advised to receive prophylactic cranial irradiation. The primary endpoint was survival, and secondary endpoints were time to progression (TTP), response, toxicity, and costs. Patient characteristics were generally well balanced in the 2 arms, even though more patients in the epirubicin/cisplatin arm had > 5% weight loss and poor Karnofsky performance index compared with the etoposide/cisplatin arm. One hundred thirty-four patients (66.3%) in the etoposide/cisplatin arm and 126 (63.0%) in the epirubicin/cisplatin arm received all 6 planned cycles of chemotherapy. Response rate, TTP, and survival did not differ significantly between the 2 arms. Grade 3/4 neutropenia and toxic deaths occurred more frequently in the etoposide/cisplatin arm. Epirubicin/cisplatin showed a similar activity with a slightly lower toxicity profile than the reference regimen of etoposide/cisplatin. The epirubicin/cisplatin regimen may be recommended in the treatment of SCLC.     

丝裂霉素加顺铂治疗难治性晚期乳腺癌

Objective： The mitomycin C and cisplatin combination was investigated in patients with advanced breast cancer who had been exposed to anthracyclines, vinorelbine and taxanes. Methods： Three-weekly regimen consisted of mitomycin, 6 mg/m^2 administered intravenously on day 1, and cisplatin, 25 mg/m^2 intravenously on day 1-3. Results： Thirty-eight patients aged 25-75 years （median, 46 years） were treated with an overall response rate of 31.6%. The median time to progression （TTP） was 4.0 months. Median TTP for 12 patients with a complete or partial response was 9.0 months, while stable disease and progression of disease 4.0 months, P=0.002. Grade 3/4 side effects of neutropenia, thrombocytopenia and nausea/vomiting were documented in 4 （10.5%）, 4 （10.5%） and 3 （7.9%） patients, respectively. The median overall survival was 13＊ months. Conclusion： Mitomydn C/cisplatin doublet showed antitumor activity for anthracydine-, vinorelbine- and taxane-resistant breast cancer comparable to other regimens. This well-tolerated regimen provides an affordable option for patients in China.     

Phase II trial of cisplatin/etoposide and concurrent radiotherapy followed by paclitaxel/carboplatin consolidation for limited small-cell lung cancer: Southwest Oncology Group 9713.

PURPOSE: Limited small-cell lung cancer (LSCLC) is characterized by a high initial response rate to chemoradiotherapy, but local or systemic relapse occurs in the majority of patients. Previous Southwest Oncology Group trials in LSCLC have utilized cisplatin and etoposide (PE) delivered concurrently with thoracic radiotherapy followed by two consolidation cycles. Newer chemotherapy regimens such as paclitaxel and carboplatin are active in small-cell lung cancer and hold the promise of improving both local and systemic control. S9713 evaluated the substitution of paclitaxel and carboplatin for PE consolidation in LSCLC. PATIENTS AND METHODS: Between July 1998 and August 1999, 96 patients were accrued from 43 institutions. Eighty-nine patients were eligible; 87 were assessable for survival and response. Treatment consisted of cisplatin 50 mg/m(2) on days 1, 8, 29, and 36, and etoposide 50 mg/m(2) on days 1 to 5 and days 29 to 33, with concurrent radiotherapy of 61 Gy beginning on day 1. Consolidation therapy was carboplatin (area under the curve = 6) and paclitaxel 200 mg/m(2), both drugs administered on day 1 of a 21 day cycle for three cycles. RESULTS: The response rate was 86% (complete response, 33%; partial response, 53%). Median overall survival was 17 months (95% CI, 12.7 to 19.0). One- and 2-year overall survivals were 61% and 33%, respectively. Median progression-free survival (PFS) was 9 months, 1-year PFS was 40%, and 2-year PFS was 21%. CONCLUSION: Consolidation therapy with paclitaxel and carboplatin in LSCLC resulted in an outcome similar to that seen in prior Southwest Oncology Group trials. This study and others which have tested paclitaxel in small-cell lung cancer dampens enthusiasm for this agent in the primary management of LSCLC.     

Irinotecan monotherapy offers advantage over combination therapy with irinotecan plus cisplatin in second-line setting for treatment of advanced gastric cancer following failure of fluoropyrimidine-based regimens

The optimal regimen of chemotherapy for gastric cancer in a second-line setting remains to be clarified. The aim of this retrospective study was to evaluate the efficacy and safety of second-line irinotecan treatment. A total of 134 patients with gastric cancer who had received prior chemotherapy with fluoropyrimidine-based regimens were treated with irinotecan (150 mg/m(2) on days 1 and 15) alone every 4 weeks (Arm I) or irinotecan (70 mg/m(2) on days 1 and 15) plus cisplatin (80 mg/m(2) on day 1) every 4 weeks (Arm IP) between April, 2004 and March, 2009. Patient characteristics, response rate, progression-free survival, overall survival and safety were investigated. Of 134 patients with recurrent or unresectable gastric cancer, 92 were treated in Arm I and 42 patients in Arm IP. Overall response rate in Arm I was 8.1%, compared with 20.0% in Arm IP (P=0.65). Median progression-free survival (Arm I vs. IP; 2.6 vs. 2.7 months, P=0.73) and median overall survival (Arm I vs. IP; 9.8 vs. 8.0 months, P=0.67) did not differ between the two treatment groups. Neutropenia, leukopenia and anorexia were the most common grade 3/4 adverse events, occurring significantly more frequently in Arm IP than in Arm I (P<0.05). Irinotecan may be a key agent, and serial irinotecan monotherapy is more beneficial as compared to irinotecan plus cisplatin in the treatment of advanced gastric cancer in second-line settings. Irinotecan monotherapy is beneficial compared to irinotecan plus cisplatin in second-line settings for the treatment of advanced gastric cancer refractory to fluoropyrimidine-based regimens.     

Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732.

PURPOSE: To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity. PATIENTS AND METHODS: Eligible patients (N=587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET). RESULTS: Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET. CONCLUSION: PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.     

三种化疗方案治疗晚期非小细胞肺癌的疗效分析

目的:评价MVP(MMC VDS PDD)、NP(Vinorelbine PDD)、TP(Paclitaxel PDD)三种化疗方案治疗晚期非小细胞肺癌的疗效.方法:114例晚期非小细胞肺癌患者分为3组,MVP组36例,MMC(丝裂霉素)8mg/m2,静脉推注,d1;Vindesine(长春地辛)3mg/m2,静脉点滴,d1,8;PDD(顺铂)80mg/m2,静脉点滴,d3.NP组4l例,Vinorelbine(长春瑞宾)25mg/m2,静脉点滴,d1,8,PDD 80mg/m2,静脉点滴,d3.TP组37例,Paclitaxel(紫杉醇)175mg/m2,静脉点滴,d1,PDD 80mg/m2,静脉点滴,d3.每4周为1周期,至少2周期.结果:MVP、NP及TP的有效率分别为33.2%、34.1%、40.5%;中位生存期分别为8.2个月、7.1个月、9.1个月;1年生存率分别为30.5%、34.1%、37.8%.主要不良反应MVP组为骨髓抑制及恶心、呕吐;NP组为骨髓抑制、恶心、呕吐及静脉炎;TP组为骨髓抑制、恶心、呕吐、肌肉关节疼痛及脱发.结论:MVP、NP及TP化疗方案在治疗晚期非小细胞肺癌的有效率、中位生存期及1年生存率相似,毒性可耐受.     

Randomized trial of treatment with cisplatin and interleukin-2 either alone or in combination with interferon-alpha-2a in patients with metastatic melanoma: a Federation Nationale des Centres de Lutte Contre le Cancer Multicenter, parallel study

BACKGROUND: The objective of the current study was to evaluate the response rate, survival, and toxicity of treatment with cisplatin and high dose intravenous continuous infusion interleukin-2 (IL-2) with or without interferon-alpha-2a (IFN) in patients with metastatic melanoma. METHODS: One hundred and seventeen patients with metastatic melanoma randomly were assigned to receive cisplatin, 100 mg/m2, followed after a 3-day rest period by IL-2, 18 x 10(6) IU/m2, on Days 3-6 and Days 17-21 (Arm 1) or cisplatin and IL-2 using an identical schedule plus subcutaneous IFN, 9 x 10(6) U, 3 times a week during IL-2 administration (Arm 2). In the absence of disease progression or undue toxicity, the cycle could be repeated on Day 29. Patients who responded after two cycles eventually could receive a third cycle. One hundred and one patients were evaluable for toxicity and efficacy. RESULTS: On treatment Arm 1, 3 patients (6%) achieved a complete response (CR) and 5 patients (10%) achieved a partial response (PR) with a median response duration of 3.8 months for the CRs and 8.7 months for the PRs. On treatment Arm 2, 2 patients (3%) achieved a CR (durations of 5.9 and 33.1 months, respectively) and 11 patients (21%) a PR with a median response duration of 8.3 months. The median durations of overall survival were 10.4 months (range, 1.1-39.7+ months) and 10.9 months (range, 0.5-38.1+ months) for treatment Arms 1 and 2, respectively. The toxicity profile was consistent with the known side effects of this IL-2 intravenous regimen combined with cisplatin chemotherapy and IFN. Toxicity was more pronounced in treatment Arm 2 compared with treatment Arm 1. There were 2 and 4 patients, respectively, in treatment Arms 1 and 2 who died within 28 days after completion of treatment. CONCLUSIONS: The observed overall response rates of 16% and 25% in treatment Arms 1 and 2, respectively, is lower than that expected with biochemotherapy; despite the fact that the objective of the trial was not to show any difference between the 2 treatment arms, our results indicate that the addition of IFN, at the dose and schedule used in this trial, fails to improve the activity of a cisplatin/IL-2 regimen significantly in patients with metastatic melanoma. Although response rates were relatively low, the median overall survival was nearly 1 year in both groups.     

Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer.

BACKGROUND: Amrubicin, a totally synthetic 9-amino-anthracycline, demonstrated excellent single-agent activity for extensive-stage small-cell lung cancer (ED-SCLC). The aims of this trial were to determine the maximum-tolerated doses (MTD) of combination therapy with amrubicin and cisplatin, and to assess the efficacy and safety at their recommended doses (RD). PATIENTS AND METHODS: Eligibility criteria were patients having histologically or cytologically proven measurable ED-SCLC, no previous systemic therapy, an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Amrubicin was administered on days 1-3 and cisplatin on day 1, every 3 weeks. RESULTS: Four patients were enrolled at dose level 1 (amrubicin 40 mg/m(2)/day and cisplatin 60 mg/m(2)) and three patients at level 2 (amrubicin 45 mg/m(2)/day and cisplatin 60 mg/m(2)). Consequently, the MTD and RD were determined to be at level 2 and level 1, respectively. The response rate at the RD was 87.8% (36/41). The median survival time (MST) was 13.6 months and the 1-year survival rate was 56.1%. Grade 3/4 neutropenia and leukopenia occurred in 95.1% and 65.9% of patients, respectively. CONCLUSIONS: The combination of amrubicin and cisplatin has demonstrated an impressive response rate and MST in patients with previously untreated ED-SCLC.     

Docetaxel and gemcitabine combination,as first-line treatment,in patients with extensive disease small-cell lung cancer. A phase II study of the Hellenic Cooperative Oncology Group

There is some evidence that taxanes and gemcitabine are effective antitumor agents against small-cell lung cancer (SCLC). A total of 20 chemotherapy-naive patients with extensive disease (ED) SCLC, were treated as a part of the first step of a phase II study, with docetaxel 50 mg/m(2) and gemcitabine 1000 mg/m(2), both administered on day 1 and 8 every 3 weeks up to a total of six cycles. For patients who progressed after the first cycle or had stable disease after the second cycle of chemotherapy, protocol treatment was stopped and further treatment with the standard cisplatin or carboplatin-etoposide combination was administered. Patients were in the vast majority male smokers with a good performance status. A total of 72 cycles was delivered while patients managed to receive the 78 and 84% of the planned dose of docetaxel and gemcitabine, respectively. Only six patients responded partially and the trial ended prematurely since at least seven responses were required among the first 19 patients. With a median follow-up of 13 months, median time to progression (TTP) was 8 months and median survival 9.6 months. Hematological and non-hematological toxicity was generally acceptable while patients tolerated their treatment reasonably well. In conclusion, docetaxel-gemcitabine showed a modest response rate in chemotherapy-naive patients with ED SCLC.     

The clinical effect of medroxyprogesterone (MPA) in elderly patients with lung cancer

Eighty-nine patients over 70 years old with untreated lung cancer, of various cell type and in various stages, were randomly assigned to chemotherapy (CT) alone or CT combined with medroxyprogesterone acetate (MPA). CT consisted of cisplatin, 60 mg/m2 i.v., along with etoposide (VP-16), 150 mg/m2 i.v., on day 1. The VP-16 was increased to 200 mg/m2, orally, on day 3. The entire regimen was given every 4 weeks for a maximum of six cycles. MPA was administered in daily 500-mg doses, i.m., 5 days a week for 1 month, followed by 1000 mg i.m., once a week, for 5 months. Changes in body weight and appetite were documented. After two cycles of CT, 64 patients were found to be evaluable for response. Forty-five had non-small-cell lung cancer (NSCLC) and 19 had small-cell lung cancer (SCLC). Thirty-seven patients had received CT alone and 27 CT plus MPA. In NSCLC, the objective response to CT alone was 36% versus 37% with CT plus MPA. In SCLC, the corresponding figures were 63% and 22%. The overall objective response rate was 60% in NSCLC and 48% in SCLC. Median survival using CT alone was 10 months for NSCLC patients and 11 months for SCLC patients. Using CT plus MPA, it was 10 months for NSCLC patients and 7 months for SCLC patients. In the control arm, 1-year survival was 42% for NSCLC patients and 48% for SCLC patients; in those who were given MPA, it was 48% for NSCLC patients and 9% for SCLC patients. Improved appetite and weight gain were reported more frequently by MPA patients, and they did not complain of CT's usual side effects. The fact that MPA had no significant effect on CT response or survival in patients also treated with a combination of cisplatin and VP-16, along with the small survival advantage for the control group in SCLC patients, suggests that combining MPA and CT may result in improved quality of life.