A phase II trial of carboplatin in untreated patients with extensive stage small cell lung cancer.

Twenty-five untreated patients with extensive stage small cell lung cancer (ESSCLC) were treated with carboplatin (CBDCA) (500 mg/m2) given as a 24-hour infusion every 21 days. Thirteen patients responded for an overall response rate of 52% (95% confidence limits, 32% to 72%) with 3 complete responses (CR) (12%; 95% confidence limits, 0% to 25%). The median duration of response was 4.5 months. The median survival time was 8 months with three long-term survivors (12%) at 27, 33, and 43 months from the start of CBDCA treatment. Ninety-two courses of CBDCA were administered and one treatment-related death occurred. The main toxicity was myelosuppression. Grade 3 or 4 hematologic toxicity (hemoglobin level, less than 8 g/dl; granulocyte count, less than 1900/microliters; and platelet count, less than 49,000/microliters) was observed as follows: neutropenia in 7 courses (8%) and in 7 patients (28%), decreased hemoglobin level in 13 courses (15%) and in 7 patients (28%), and decreased platelet count in 10 courses (11%) all Grade 3 and in 8 patients (32%). This study demonstrates that at this dose and schedule CBDCA is a highly active drug in ESSCLC and it has tolerable toxicity.     

Cisplatin-etoposide alternating with topotecan in patients with extensive stage small cell lung cancer (SCLC). A multicenter phase II study

The objective of the study was to find out whether the delay in time from when bronchogenic carcinoma is diagnosed until a therapeutic thoracotomy is performed affects patient survival. The population analysed comprised 1082 patients with clinical stage I and II, non-small cell lung cancer (NSCLC), who had been operated on between October 1993 and September 1997, and were registered in the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). In this series, the median therapeutic delay was 35 days (1-154), with a median survival rate of 52 months (45.6-58.3). A statistical study was developed that, in addition to the delay, included the variables of age, histology, clinical stage, and pathological stage of the disease. Therapeutic delay was included in the multivariable analysis as a quantitative and qualitative variable and a comparison among the different intervals of delay in days (1-20 vs. 21-40 vs. 41-60 vs. > 60) was performed in order to ascertain its influence on survival. Univariate and multivariate Cox's regression analyses showed that age (> 70 years), clinical stage (I vs. II), and pathological stage influence survival. As for the histology and the delay, no significant differences were observed in the survival of any of the intervals even when compared against the intervals at the extremes (1-20 vs. > 60). In conclusion we found no influence of delay upon the survival.     

Sequential administration of cisplatin-etoposide followed by topotecan in patients with extensive stage small cell lung cancer. A multicenter phase II study

PURPOSE: To evaluate the activity of the sequential administration of cisplatin-etoposide (PE) followed by topotecan (TOP) in patients with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated patients with extensive stage SCLC received 4 cycles of cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 every 21 days followed by 4 cycles of TOP 1.5 mg/m(2) IV on days 1-5 every 21 days. RESULTS: Thirty-eight patients were entered in the study. Their median age was 63 years and the performance status (WHO) was 0 for 5, 1 for 25 and 2 for 8 patients. All patients were evaluable for toxicity and 32 for response to PE and 25 to TOP. Of the 38 patients receiving PE, 1 (3%) patient achieved complete response (CR) and 17 (45%) partial responses (PR) for an overall response rate to PE of 47% (95% confidence interval: 36.7-68.5%). Four (23.5%) of the 17 patients with PR after PE, achieved CR with TOP. None of the patients with stable or progressive disease after PE responded to TOP. The response rate of the 27 patients receiving TOP following PE was 15% (95% confidence interval: 1.4-28.2%). After a median follow up of 9 months, the median duration of response was 6.5 months, the time to tumor progression 6.5 months, the median survival 8.5 months and the 1-year survival 34%. A total of 136 cycles of PE and 89 cycles of TOP have been administered with a median of 4 cycles/patient for each regimen. There were 2 toxic deaths after PE associated with grade IV febrile neutropenia. Treatment delays due to toxicity occurred in 17 (12%) cycles of PE and 20 (22%) cycles of TOP while doses were reduced in 7 (5%) and 4 (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia occurred in 24, 2 and 3% of PE cycles and 21, 12 and 1% of TOP. Non-hematologic toxicity was mild. The delivered dose intensity was 100% for PE and 93% for TOP. CONCLUSIONS: The sequential administration of TOP after PE is associated with manageable toxicity and may increase the number of CRs in patients with chemosensitive extensive stage SCLC. However, based on this data and the lack of survival benefit in a previous phase III study, the sequential regimen should not be used outside of a clinical trial.     

Carboplatin plus paclitaxel in extensive small cell lung cancer: a multicentre phase 2 study

A multicentre phase 2 trial (single-stage design) was undertaken to test the efficacy and toxicity of carboplatin (AUC 6 according to Calvert) plus paclitaxel (175 mg/m(2)3-h infusion) every 4 weeks in the first line treatment of patients affected by extensive small cell lung cancer. The primary end-point of the trial was the objective response rate. 31 objective responses among 50 patients were considered necessary to proceed to a phase 3 trial. 48 patients were enrolled (median age 59 years). Treatment was very well tolerated. 3 patients (6.2%) had a complete response and 23 (47.9%) a partial response, for an overall response rate of 54.2% (95% CI: 39.2-68.6). Median time to progression was 5.7 months (95% CI: 5.2-6.2). Median survival was 9.6 months (95% CI: 7.2-14.6), with a median follow-up time of alive patients of 12 months. At 1 year, the probability of being progression-free or alive was 0.16 and 0.43, respectively. In conclusion, carboplatin plus paclitaxel as given in the present study is very well tolerated but not sufficiently active to warrant phase 3 comparison with standard chemotherapy regimens.     

A phase I study of paclitaxel, etoposide, and cisplatin in extensive stage small cell lung cancer.

This Phase I study was designed to determine the maximally tolerated dose (MTD) of paclitaxel with standard doses of cisplatin and etoposide for patients with untreated extensive stage small cell lung cancer (SCLC). Secondary objectives were to determine the toxicities, response rate, response duration, and overall survival in this cohort. Twenty-eight SCLC patients were enrolled into four dose levels. All patients received a fixed dose of cisplatin at 80 mg/m2, i.v., day 1. The first group received etoposide 50 mg/m2, i.v. day 1 and 100 mg/m2 p.o., days 2-3, whereas all subsequent groups received etoposide 80 mg/m2, i.v., day 1 and 160 mg/m2, p.o., days 2-3. The paclitaxel starting dose was 135 mg/m2, i.v., over a 3-h period and was escalated to 175 and 200 mg/m2. Cycles were repeated every 21 days for a maximum of six cycles. Granulocyte-colony stimulating factor was not given prophylactically but was allowed in subsequent cycles according to the American Society of Clinical Oncologists guidelines. All 28 SCLC patients were evaluable for toxicity, and 23 patients were evaluable for response. Myelosuppression was the major toxicity, with grade 4 neutropenia occurring in 23 of 28 patients (82%), but febrile neutropenia was uncommon and developed in 4 patients (14%). Grade 4 thrombocytopenia and anemia were rare, occurring as isolated events in one patient each. Dose-limiting peripheral neuropathy was observed at a paclitaxel dose of 200 mg/m2. Grade 4 nausea/vomiting and diarrhea were also noted at this dose level. Five patients had complete responses (22%), and 14 patients had partial responses (61%). The overall response rate was 83% with a median time to progression of 7.5 months, a median survival of 10 months, and a 1-year survival rate of 39%. This three-drug combination of paclitaxel with cisplatin and etoposide is active with acceptable toxicity. Neurotoxicity was dose limiting at 200 mg/m2 of paclitaxel. Neutropenia was frequent but not associated with significant morbidity. The recommended doses for future clinical trials are 175 mg/m2 paclitaxel, i.v., over a 3-h period on day 1 with 80 mg/m2 cisplatin, i.v., on day 1 and 80 mg/m2 etoposide, i.v., on day 1 and 160 mg/m2 p.o. on days 2 and 3 with growth factor support. The Southwestern Oncology Group has instituted a Phase II study with this dose schedule.     

Etoposide, ifosfamide, and cisplatin in extensive small cell lung cancer.

From December 1987 through April 1989, 40 patients with extensive-stage small cell carcinoma of the lung were enrolled in a Hoosier Oncology Group (HOG) trial using etoposide, ifosfamide, and cisplatin (VIP). Patients with extensive disease were eligible if they had not received prior chemotherapy, had a Karnofsky performance status of 50 or more, and had adequate renal function (creatinine, less than 1.5 mg/dl) and bone marrow reserve (granulocyte count, greater than or equal to 2500/microliters; platelets, greater than or equal to 125,000/microliters). Doses of therapy were: etoposide 75 mg/m2/day on days 1 to 5, ifosfamide 1.2 g/m2/day on days 1 to 5, and cisplatin 20 mg/m2/day on days 1 to 5. The first 11 patients received a 5-day course; this was repeated every 21 days for four cycles, but therapy was shortened to 4 days when unacceptable toxicity was noticed in these patients. Overall, 14 (37%) had a complete remission (overall response rate, 71.1%) with a median survival of 42 weeks (28 weeks on 5-day regimen and 45 weeks on 4-day regimen). There were five early deaths. Although toxic, VIP produces a high complete remission rate in patients with extensive disease and warrants further evaluation. A prospective randomized trial comparing cisplatin and etoposide to the VIP regimen is underway through HOG.     

73例广泛期小细胞肺癌患者的预后因素分析

目的:对广泛期SCLC影响中位生存期的相关因素进行分析。方法:统计73例患者的临床资料,包括性别、年龄、肿瘤位置、PS评分、远处转移部位和治疗方法等。采用电话形式进行随访,Kaplan-Meier曲线进行单因素生存分析,生存率比较采用Log-rank检验。将有统计学意义的变量,带入COX比例风险模型进行多因素生存分析。结果:患者总体中位生存期是10.7个月。单因素分析得出,PS评分、脑转移、肝转移、常规治疗以及全脑预防性照射对患者的中位生存期有影响。多因素分析得出,PS>2分、发生肝转移和未行全脑预防照射是独立危险因素。结论:在广泛期SCLC患者中,PS>2分,发生肝转移以及未行PCI治疗的患者预后较差。在临床诊治中,应结合患者具体情况,给予合适的综合治疗。     

A phase II study of biweekly irinotecan and cisplatin for patients with extensive stage disease small cell lung cancer

BACKGROUND: An irinotecan and cisplatin (IP) combination is one of active regimen used in treatment of extensive stage disease (ED) small cell lung cancer (SCLC). However, a 4-week cycle of irinotecan treatment can result in significant myelosuppression and diarrhea. Therefore, the present study was conducted to evaluate the efficacy and safety of biweekly IP in patients with ED SCLC. METHODS: Patients with previously untreated ED SCLC received intravenous irinotecan at a dose of 60mg/m(2) and cisplatin at a dose of 30mg/m(2) on days 1 and 15 every 4 weeks. RESULTS: Thirty-five patients were enrolled in this study. Three complete responses and 23 partial responses were confirmed, giving an overall response rate of 74.3%. After a median follow-up of 15.1 months, the median time to progression and overall survival were 7.7 months and 12.2 months, respectively. Grade 3/4 neutropenia occurred in seven patients and grade 3 febrile neutropenia was observed in one patient. Grade 3 diarrhea occurred in two patients. CONCLUSIONS: The combination chemotherapy of biweekly IP was found to be well tolerated and effective in patients with ED SCLC. Further evaluation of the combination of IP at the dose and schedule in this study is warranted in ED SCLC patients.     

A phase II trial of the Src-kinase inhibitor saracatinib after four cycles of chemotherapy for patients with extensive stage small cell lung cancer: NCCTG trial N-0621

Introduction

To assess the efficacy and the Src-kinase inhibitor saracatinib (AZD-0530) after four cycles of platinum-based chemotherapy for extensive stage small cell lung cancer (SCLC).

Methods

Patients with at least stable disease received saracatinib at a dose of 175 mg/day by mouth until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint was the 12-week progression-free survival (PFS) rate from initiation of saracatinib treatment. Planned interim analysis in first 20 patients, where 13 or more patients alive and progression-free at 12-weeks would allow continued enrollment to 40 total patients.

Results

All 23 evaluable patients received platinum based standard chemotherapy. Median age was 58 years (range: 48–82). 96% of patients had a performance status of 0/1. Median of two cycles given (range: 1–34). All 23 (100%) patients have ended treatment, most for disease progression (19/23). The 12-week PFS rate was 26% (6/23; 95% CI: 10–48%). From start of standard chemotherapy, median PFS was 4.7 months (95% CI: 4.5–5.1) and median OS was 11.2 months (95% CI: 9.9–13.8). Eight (35%) and three (13%) patients experienced at least one grade 3/4 or grade 4 AE, respectively. Commonly occurring grade 3/4 adverse events were thrombocytopenia (13%), fatigue (9%), nausea (9%), and vomiting (9%).

Conclusions

Saracatinib at a dose of 175 mg/day by mouth is well tolerated. However, the PFS rate observed at the pre-planned interim analysis did not meet the criteria for additional enrollment.     

Etoposide combination therapy for small cell carcinoma of the lung

Summary Sixty-three consecutive patients with small cell carcinoma of the lung were treated by six cycles at 3-week intervals of etoposide 120 mg/m² i.v. on day 1 and orally on days 2–5, adriamycin 40 mg/m² i.v. on day 1 and vincristine 1.4 mg/m² i.v. on day 1. Tumour bed irradiation was administered to patients with limited disease after chemotherapy. In limited-disease and extensive-disease patients the median survival was 12 and 6 months respectively. The 2-year survival rate (life table) in limited-disease patients was 26%. Treatment morbidity was low.A prospective randomised trial is being undertaken to further evaluate the role of oral etoposide in combination chemotherapy.     

Addition of topotecan to standard cisplatin/etoposide combination in patients with extended stage small cell lung carcinoma

BACKGROUND: Topotecan is an active agent for the management of untreated and recurrent extensive-disease small cell lung cancer (ED-SCLC). This study was designed to evaluate the efficacy and safety of a triplet combination with topotecan added to the standard PE regimen in previously untreated patients with ED-SCLC. MATERIALS AND METHODS: Twenty-one patients (median age 55 years, and 18 male) with chemotherapy-naive ED-SCLC were enrolled into the study. PET treatment consisted of etoposide 80mg/m(2), cisplatin 20mg/m(2) and topotecan 0.75mg/m(2) and all were given intravenously on days 1 to 3 for every 3 weeks. RESULTS: Leucopoenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Severe leucopenia/neutropenia were observed in 14 (67%)/12 (57%) patients, and only two (10%) developed febrile neutropenia. Severe thrombocytopenia was observed in 6 (29%) patients and one patient died due to orbital and cerebral haemorrhage. Dose reductions were required in 13 (62%) patients, delays in 8 (38%) patients and early treatment discontinuation in 3 (14%) patients. The overall response rate was 52.6% (95% CI: 28, 9-75.6) with 2 (10.5%) complete and 8 (42.1%) partial responses. The overall median survival time was 6.6 months (range 0.5-16.5 months) and the 6-month overall survival was 65.3%+/-11.7. The overall median survival time of responders was 9.7 months compared to 5.7 months in non-responders (p=0.026). CONCLUSION: Topotecan combined with PE regimen with this schedule and dosage does not seem to provide any benefit in terms of response and survival in ED-SCLC patients and does not deserve further studies.     

66例广泛期小细胞肺癌患者预后分析

目的:分析广泛期小细胞肺癌的独立预后因素。方法:回顾性分析安阳市肿瘤医院2005年7月至2009年7月治疗的66例广泛期小细胞肺癌的临床资料,所有患者均经组织病理或细胞学确诊。生存分析采用Kaplan-Meier法计算生存率,Log-rank检验进行单因素分析,并对有意义的单因素通过COX风险模型筛选影响预后因素。结果:广泛期患者1、2、3年生存率分别为40.9%、13.6%、6.1%,中位生存时间为10个月。单因素分析显示体重减轻情况、一线化疗疗效、总化疗周期数、治疗方式、低钠血症与患者预后相关,具有统计学差异。多因素分析显示一线化疗疗效、总化疗周期数、低钠血症对患者的总生存时间具有显著影响。结论:一线化疗疗效、总化疗周期数和低钠血症是影响广泛期小细胞肺癌的独立预后因素。     

Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer

BACKGROUND

Preclinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models.

METHODS

We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response.

RESULTS

Thirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade &ge;2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD) &ge;6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD&ge;6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD&ge;6 months or uPR. Correlation between grade of rash and rate of SD&ge;6 months/PR was observed (p<0.01).

CONCLUSION

The combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC.     

Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial

BACKGROUND: Cisplatin-containing regimens represent the gold standard in the treatment of advanced non-small cell lung cancer, but carboplatin is often preferred for its better toxic profile when palliation is the aim of the treatment. The synergistic effect and tolerability of carboplatin-gemcitabine combination are well known. In this phase II trial, we evaluated the activity and safety of a schedule with carboplatin and gemcitabine, defined in our previous phase I trial. METHODS: Thirty-seven patients with measurable stage IV non-small cell lung cancer were treated with carboplatin, AUC 4.5 mg/ml/min on day 1, and gemcitabine, 800 mg/m2 on days 1 and 8, every 21 days. All patients were treated until disease progression or intractable toxicity and were evaluated before each course of chemotherapy for toxicity and after every 3 courses for response. RESULTS: After a median follow-up of over 10 months, complete response, partial response, and stabilization of the disease were observed in 3 (8.1%), 9 (24.3%), and 15 patients (40.5%), respectively. Median time to progression was 7 months. At this writing, 27 patients have died, with a median survival of 10 months, and 29 (78.3%), 16 (43.2%), and 11 (29.7%) patients are alive after 6, 12, and 15 months of follow-up, respectively. Toxicity was mild, and mainly hematological, with a significant correlation with the number of courses of chemotherapy (P = 0.0003). CONCLUSIONS: Our results are comparable with those reported in the literature and confirm the good activity and tolerability of the carboplatin-gemcitabine combination. Up to 4 courses of chemotherapy with carboplatin and gemcitabine may represent an interesting option in the palliative treatment of non-small cell lung cancer.     

Salvage treatment with topotecan in patients with irinotecan-refractory small cell lung cancer

Purpose  Although the efficacy of topotecan as a second-line chemotherapy for small-cell lung cancer (SCLC) has been consistently demonstrated in phase II/III clinical trials, the choice of irinotecan as the first-line therapy prevented the use of evidence-based option. This pilot study was conducted to determine the activity and safety of topotecan in SCLC patients refractory to first-line therapy with irinotecan and platinum. Methods  Patients with primary refractory (no response, or progression during or ≤90 days after last chemotherapy) SCLC after treatment with a combination of irinotecan and platinum, received topotecan 1.5 mg/m² per day as a 30-min infusion daily for 5 days, every 3 weeks. Results  Of 17 eligible patients, ten patients were previously treated with irinotecan plus cisplatin and 7 were treated with irinotecan plus carboplatin. The median age was 68 years (range 44–75) and the median interval from the last chemotherapy was 50 days (range 21–89). A total of 33 chemotherapy cycles were delivered (median 2; range 1–5). All 17 patients discontinued therapy due to disease progression and 5 patients had progressive disease before second cycle. Toxic effects were mainly hematologic (grade ≥3 neutropenia in 65% of patients) and fatigue (grade 3 in 47%). In an intent-to-treat analysis, two (12%) patients had a confirmed partial response and two patients achieved stable disease. Median progression-free and overall survivals were 1.7 months (95% CI, 1.5–1.9) and 3.4 months (95% CI, 1.7–5.0), respectively. Conclusions  Topotecan monotherapy for patients with irinotecan-refractory SCLC does not appear highly active but the observation of some responses merits further study in patients with chemosensitive disease.     

A phase I study of topotecan/paclitaxel alternating with etoposide/cisplatin and thoracic irradiation in patients with limited small cell lung cancer.

PURPOSE: Topotecan and paclitaxel are promising cytotoxic drugs with novel mechanisms of action relative to other chemotherapies used in the treatment of small cell lung cancer (SCLC). In an effort to integrate paclitaxel and topotecan into the treatment of limited disease (LD) SCLC, we conducted a Phase I study of these agents administered as initial induction therapy. EXPERIMENTAL DESIGN: Escalating doses of topotecan (0.8-1.4 mg/m(2) d1-5) and paclitaxel (110-175 mg/m(2) d1) were administered i.v. every 21 days for two cycles to determine the maximum tolerated dose (MTD) in patients with LD SCLC. This was followed by two cycles of etoposide (120 mg/m(2) d1-3) and cisplatin (60 mg/m(2) d1) with thoracic radiotherapy. The first 5 subjects received 1.8 Gy once daily x 25 fractions, while subsequent subjects received 1.5 Gy twice daily x 30 fractions. Two additional cycles of chemotherapy (topotecan and paclitaxel, followed by etoposide and cisplatin) were given. RESULTS: Common toxicities included grade >/=3 neutropenia in 67% of courses of topotecan and paclitaxel and grade >/=2 esophagitis in 71% of patients. The MTD was based on toxicity during the first two cycles of chemotherapy and defined after accrual of 18 patients to four dose levels. Two of three patients developed grade 3 nonhematological toxicity (pneumonia) at the fourth dose level. Thus, the third dose level (topotecan 1.2 mg/m(2), paclitaxel 160 mg/m(2)) was defined as the MTD recommended for Phase II studies. One subject died suddenly on day 2 of cycle 1 without autopsy confirmation of the etiology. A second subject died during cycle 3 due to thrombocytopenia, gastrointestinal bleeding, and respiratory failure. Response rates after induction of topotecan and paclitaxel: 16 of 18 (88.8%) partial response, 1 of 18 (5.5%) complete response. Response rates after completion of therapy: 10 of 18 (55.5%) partial response, 7 of 18 (38.8%) complete response. CONCLUSIONS: Induction topotecan and paclitaxel before chemoradiotherapy in patients with LD SCLC is feasible and results in expected toxicities. The outcome of a recently closed Cancer and Leukemia Group B Phase II study of similar design (CLB-39808) should help determine whether or not this approach warrants testing in a randomized setting.     

A multi-center phase II study of weekly topotecan as second-line therapy for small cell lung cancer

PURPOSE: To determine the response rate, toxicity, failure free and overall survival of weekly topotecan in patients with relapsed small cell lung cancer who received one prior platinum based chemotherapy. PATIENTS AND METHODS: Twenty two patients with relapsed disease after response to one prior chemotherapy with or without radiotherapy and patients with relapse more than 90 days after their last therapy received topotecan 4mg/m(2) intravenous over 30min on days 1,8,15; every 4 weeks (3 weeks on and 1 weeks off). Chemotherapy was given until disease progression or unacceptable toxicity. RESULTS: Of 22 patients, none of the patients responded to weekly topotecan therapy. Four patients had stable disease. After a median follow up of 1 year, median time to progression was 6 weeks and median survival was 5 months. The common toxicities associated with this regimen were anemia, thrombocytopenia, fatigue, GI side effects and alopecia. CONCLUSION: Weekly topotecan was well tolerated but ineffective in this trial. Although commonly used, weekly regimen of topotecan should be used with caution in relapsed SCLC.