A phase II trial of cisplatin and prolonged administration of oral etoposide in extensive-stage small cell lung cancer.

Etoposide is a schedule-dependent agent with greater activity against small cell lung cancer (SCLC) when a given dose is administered over several days compared with a 1-day administration of the same dose. In an attempt to capitalize on the schedule dependency of etoposide, 22 previously untreated extensive-stage SCLC patients were given cisplatin (100 mg/m2 on day 1) plus 21 days of low-dose, oral etoposide (50 mg/m2/d). Chemotherapy was repeated every 28 days for four cycles. Complete blood counts were monitored weekly, and etoposide was discontinued if either the leukocyte or platelet count dropped below 2000/microliters or 75,000/microliters, respectively. All 22 patients were evaluable for response; 18 had either a complete (9%) or partial response (73%), an overall response rate of 82% (95% confidence interval, 62% to 93%). The median response duration was 7 months, and the median survival was 9.9 months (range, 1 to 17+ months). Sixteen (73%) patients received all planned cycles of etoposide. In Cycle 1 of chemotherapy, the median leukocyte nadir was 2700/microliters (range, 100 to 6300/microliters), and median platelet nadir was 180,000/microliters (range, 51,000 to 397,000/microliters). Life-threatening leukopenia (less than 1000/microliters) was rare (3 of 74 cycles). There were three treatment-related deaths, only one of which was associated with neutropenia. One patient had mild renal insufficiency that resolved after discontinuation of therapy. Alopecia was observed in all patients, but other nonhematologic toxicities were uncommon. A randomized study is necessary to determine if this schedule of cisplatin and etoposide administration is superior to more standard methods. However, these data do not indicate a major survival benefit will be derived from increasing the duration of etoposide administration when used in combination with cisplatin given every 28 days.     

Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial

PURPOSE: To compare the combination of paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and topotecan (Hycamtin; Glaxo SmithKline, Philadelphia, http://www.gsk.com) with paclitaxel, carboplatin (Paraplatin; Bristol-Myers Squibb), and etoposide (Etopophos, VePesid; Bristol-Myers Squibb) in patients with previously untreated extensive-stage small cell lung cancer. PATIENTS AND METHODS: In this phase II trial, 120 patients were randomly allocated to receive either topotecan (1.5 mg/m(2) i.v. days 1, 2, and 3) and paclitaxel (175 mg/m(2) i.v. day 1) every 21 days orpaclitaxe l (200 mg/m(2) i.v. day 1), carboplatin (area under the concentration-time curve 6 i.v. day 1), and etoposide (50 mg/100 mg alternating daily by mouth days 1-10) every 21 days, each regimen for a maximum of eight cycles. The primary end points were objective response rate and time to progression. RESULTS: The paclitaxel-carboplatin-etoposide combination produced a significantly higher overall response rate (78% versus 48%), longer median time to progression (7.6 months versus 5.5 months), and greater number of patients free from progression at 1 year (14% versus 8%) compared with paclitaxel plus topotecan. There was no difference in overall survival. Toxicities were similar in the two treatment arms. CONCLUSIONS: The paclitaxel-carboplatin-etoposide combination produced a superior overall response rate and time to progression in patients with extensive-stage small cell lung cancer compared with paclitaxel plus topotecan. The platinum compounds continue to be a necessary component of the initial therapy for these patients.     

Phase II study of cisplatin/etoposide and endostar for extensive-stage small-cell lung cancer

Purpose  

To investigate the efficacy and safety of endostar, a novel recombinant human endostatin, plus cisplatin, and etoposide in patients with extensive-stage small-cell lung cancer (ED-SCLC).     

Randomized comparison of lobaplatin plus etoposide and cisplatin plus etoposide chemotherapy in patients with extensive-stage small cell lung cancer

Objective

To compare the efficacy and safety of Lobaplatin plus Etoposide (EL) and Cisplatin plus Etoposide (EP) regimens in chemonaive with extensive-stage small-cell lung cancer (SCLC).

Methods

Between July 2010 and July 2011, a total of 62 patients with extensive-stage small-cell lung cancer who received initial treatment in our hospital and 309 hospital of PLA. 31 patients were randomly assigned to the EL Group: Lobaplatin was given intravenously at a dose of 30 mg/m² on day 1 and Etoposide 100 mg/m² on days 1 to 3 of 21-day cycles for a maximum of six cycles. Another 31 patients were assigned to the EP Group: Cisplatin was given intravenously at a dose of 75 mg/m² on day 1 and Etoposide 100 mg/m² on days 1 to 3 of 21-day cycles for a maximum of six cycles. We evaluated the efficacy, overall response rate (ORR), disease control rate (DCR), the progression-free survival (PFS) and toxicity between the patients of the two groups.

Results

All 62 patients were eligible. In the EL group, 2 (6.5%) patients had complete response, 20 (64.5%) patients had partial response, 5 (16.1%) patients had stable disease and 4 (12.9%) patients had progress disease. In the EP group, 2 (6.5%) patients had complete response, 22 (70.9%) patients had partial response, 4 (12.9%) patients had stable disease and 3 (9.7%) patients had progress disease. The ORR of EL and EP group were 70.9% and 77.4%, respectively, showing no significant difference (P = 0.562). The DCR of both groups were 87% and 90%, respectively, showing no significant difference (P = 0.688). Median PFS of patients with EL and EP regimens were 5.5 months and 5 months, respectively, showing no significant difference (P = 0.637). Adverse events were observed in all 62 patients. Grade 1 to 4 anemia was higher in the EP group than in EL group, showing significant difference (P = 0.02). Grade 3 and 4 thrombocytopenia was seen in 4 patients (12.9%) in EL group and 1 patient (3.2%) in EP group. Although one patient had platelet transfusion owing to Grade 4 thrombocytopenia in EL group, no significant difference (P = 0.637) were shown. The incidence of nausea/vomiting was higher in the EP group than in the EL group (96.7% vs 51.6%, P = 0.00).

Conclusion

The EL regimen is an effective and low-toxicity chemotherapy and no inferior to EP regimen in treatment response, therefore, EL regimen maybe is a good choice for patients with extensive-stage SCLC.     

E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer

Purpose

Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC).

Methods

Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0–3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m²) on days 1, 2 and 3, etoposide (70 mg/m²) and cisplatin (20 mg/m²) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m²) and cisplatin (20 mg/m²) on days 1 and 8 followed by etoposide (85 mg/m² PO bid) on days 3 and 10 (PIE) in a 3-week cycle.

Results

We enrolled 140 patients and randomized 66 eligible patients to each arm. Only 54.5 % of all patients completed the planned maximum 6 cycles. There were grade ≥3 treatment-related adverse events in approximately 70 % of the patients on both arms including 6 treatment-related grade 5 events. The overall response rates (CR + PR) were 69.7 % (90 % CI 59.1–78.9, 95 % CI 57.1–80.4 %) for arm A and 57.6 % (90 % CI 46.7–67.9, 95 % CI 44.8–69.7 %) for arm B. The median progression-free survival and overall survival were 6.4 months (95 % CI 5.4–7.5 months) and 11.9 months (95 % CI 9.6–13.7 months) for arm A and 6.0 months (95 % CI 5.4–7.0 months) and 11.0 months (95 % CI 8.6–13.1 months) for arm B.

Conclusion

Sequential administration of topoisomerase inhibitors did not improve on the historical efficacy of standard platinum-doublet chemotherapy for extensive-stage SCLC.     

Progressive disease rate as a surrogate endpoint of phase II trials for non-small-cell lung cancer

Background: Although the potential activity of anticancer agents has been traditionally assessed by the response rate (RR) in phase II trials, there is an increasing need to identify alternative endpoints to evaluate the efficacy of novel types of antineoplastic agents such as cytostatic agents. However, none of the proposed alternatives have been validated.Design: RR, rate of progressive disease (PD), and median survival time (MST) were obtained from 44 treatment arms in 42 single-agent phase II trials for non-small-cell lung cancer (NSCLC). Correlations between these parameters and their significance in selection of promising drugs were evaluated.Results: The median (range) RR and PD rate per treatment arm were 17% (0%–40%) and 41% (8%–93%), respectively. The PD rate correlated more closely with MST (correlation coefficient (r) = 0.80, P < 0.001) than did the RR (r = 0.62, P < 0.001). The RR of active agents against NSCLC ranged broadly from 7% to 40%, whereas their PD rates were all 50% or less. In addition, all treatment arms with a PD rate over 50% had a poor MST of six months or shorter.Conclusions: The PD rate was potentially as good an endpoint as RR, and it may be a good candidate for the primary endpoint of phase II trials for novel types of anticancer agents.     

Phase II study of oral etoposide and intravenous paclitaxel in extensive-stage small cell lung cancer

BACKGROUND: This study evaluated the activity and tolerance for the combination of oral etoposide and paclitaxel as first-line therapy for patients with extensive SCLC. METHODS: A total of 57 patients were enrolled in this study. A cycle of chemotherapy consisted of oral etoposide administered as 50 mg BID on days 1 through 10 and paclitaxel administered as 150 mg/m(2) IV (3 h infusion) along with the first dose of etoposide on day 10. Patients were assessed for response to therapy (regression, stable disease, progression), survival, time to disease progression, and toxicity. RESULTS/CONCLUSIONS: Fifty-five patients were evaluable for efficacy parameters. Among the 55 patients, there were six with complete regression of disease, 18 with partial regression, 11 with regression, five with stable disease, and 15 with progressive disease, yielding an overall response rate of 63.6% (95% confidence interval, 50.0-76.0%). The 6-month and 1-year progression-free survival rates were 48.2 and 18.9%, respectively. The median time to disease progression was 5.8 months. The overall survival rates were 67.3% at 6 months and 41.8% at 1 year. The combination of oral etoposide and paclitaxel demonstrated significant efficacy as first-line therapy for extensive SCLC, with an overall response rate of 63.6% for 55 evaluable patients. In addition, the treatment was well tolerated with no unexpected toxicities.     

洛铂或顺铂联合依托泊苷治疗广泛期小细胞肺癌的临床观察

目的 探讨依托泊苷联合洛铂化疗方案治疗小细胞肺癌（SCLC）的近期疗效、远期生存及毒副反应。方法 回顾性分析未经抗肿瘤治疗的广泛期SCLC患者85例,根据治疗方案分为两组,即依托泊苷+洛铂（EL）组42例和依托泊苷+顺铂（EP）组43例。EL组给予依托泊苷80 mg／m²,d₁～d₅,洛铂30 mg／m²,d₁;EP组给予依托泊苷80 mg／m²,d₁～d₅,顺铂25 mg／m²,d₁～d₃,21天为1周期。至少完成2个周期化疗以后评估疗效和毒副反应。 结果 EL组和EP组的有效率（RR）分别为59.5％和53.5％（P＞0.05）,疾病控制率（DCR）分别为80.9％和76.7％（P＞0.05）,但EL组的中位无进展生存时间（PFS）为6.5个月,高于EP组的4.5个月（P＜0.05）。EL组血小板减少的发生率高于EP组,恶心呕吐及肝肾功能损害的发生率均低于EP组（P＜0.05）。结论 同EP方案相比,EL方案可延长中位PFS,且消化道不良反应较轻,基本无肝肾毒性。     

PET方案化疗联合胸部放疗治疗局限期小细胞肺癌的疗效观察

回顾性分析PET(Paclitaxel135mg/m2,d1,Vp-1675mg/m2d1~d3,DDP80mg/m2,d1~d3使用)方案化疗联合胸部放疗治疗局限期小细胞肺癌的临床疗效。24例局限期小细胞肺癌接受PET化疗,每3周重复1次,共4~6个周期,胸部放疗于化疗2个周期后开始进行,2Gy/(5次·周),DT50~60Gy/25~30次,治疗达完全缓解者予以全脑预防性放疗DT30Gy/(15次·3周)。结果显示,24例局限期小细胞肺癌患者完全缓解(CR)19例,部分缓解(PR)4例,总缓解率95·8%(CR79·2%,PR16·7%),中位生存期25个月,2、3年生存率分别为50·0%和41·7%,局部复发率29·2%,远处转移率54·2%。PET方案化疗联合胸部放疗治疗局限期小细胞肺癌有较好的缓解率和近期疗效,毒性反应可耐受。     

High response rate to cisplatin/etoposide regimen in childhood low-grade glioma.

PURPOSE: The aim of this study was to avoid radiotherapy and to induce an objective response in children with low-grade glioma (LGG) using a simple chemotherapy regimen based on cisplatin and etoposide. PATIENTS AND METHODS: Thirty-four children (median age, 45 months) with unresectable LGG were treated with 10 monthly cycles of cisplatin (30 mg/m(2)/d on days 1 to 3) and etoposide (150 mg/m(2)/d on days 1 to 3). Tumor originated in the visual pathway in 29 patients, in the temporal lobe in two, in the frontal lobe in two, and in the spine in one. Eight children were affected by neurofibromatosis type 1. Objective tumor response and toxicity were evaluated by magnetic resonance imaging and neurologic and functional tests at 3-month intervals. RESULTS: An objective response was obtained in 24 (70%) of 34 patients, whereas the others had stable disease. None of the children were electively irradiated. In 31 previously untreated children, overall survival was 100% and progression-free survival was 78% at 3 years, with a median follow-up of 44 months. Acute toxicity was unremarkable; 28% patients evaluated for acoustic neurotoxicity revealed a loss of perception of high frequencies. CONCLUSION: Cisplatin and etoposide combined treatment is one of the most active regimens for LGG in children and allows avoidance of radiotherapy in the vast majority of patients.     

A phase II study of weekly alternating chemotherapy in extensive-stage small cell lung cancer

Despite the recent development of new chemotherapeutic agents with activity in small cell lung cancer (SCLC), the long-term prognosis of patients with extensive-stage disease remains poor and has not improved in the past 20 years. The present study was designed to evaluate the activity and toxicity of weekly, alternating-regimen chemotherapy in patients with extensive-stage SCLC. Patients with previously untreated extensive-stage SCLC and performance status 0-2 were treated with cyclophosphamide 250 mg/m², etoposide 100 mg/m², and cisplatin 50 mg/m² on day 1; vincristine 1 mg/m² on day 8; and ifosfamide 1.2 gm/m² on days 8 and 9 with the entire treatment repeated every 14 days. Eighteen patients received chemotherapy for a median of 14 weeks (range, 1-35 weeks). Seventeen patients (94%) required dose delays and 16 patients (89%) required at least one dose reduction due to toxicity. Twelve patients (67%) exhibited an objective response (1 complete response, 11 partial response) with a median duration of response of 18 weeks (range, 8-32 weeks). Median survival was 33 weeks (range, 1-57 weeks) with a 1-year survival rate of 22%. Toxicity was primarily hematologic, including grade 3-4 leukopenia (82% of patients) and anemia (53% of patients). Only 2 patients developed grade 3 peripheral neuropathy and none exhibited grade 3-4 renal insufficiency. This regimen of weekly alternating combination chemotherapy resulted in tolerable toxicity as well as response and survival rates comparable to those achieved with standard chemotherapy in patients with extensive-stage SCLC. However, weekly chemotherapy regimens for the treatment of SCLC remain investigational.     

Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

Objective In this study, we evaluated the difference of progression-free survival(PFS) and overall survival(OS) between extensive-stage small-cell lung cancer(ES-SCLC) patients who acquired partial response(PR) or complete remission(CR) after two cycles of first-line chemotherapy with the etoposide plus cisplatin(EP) regimen and those who acquired PR or CR after four or six cycles.Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region(China) between November 2004 and May 2011, were enrolled in this study. RECIST version 1.1 was used for the evaluation of chemotherapy efficiency. We followed up all eligible patients every 4 weeks. All statistical data were analyzed by using SPSS 21.0 statistical package for Windows.Results After a median follow-up of 293 days(range, 62–1531 days), all patients had died by the cutoff date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months(95% CI, 5.1–6.9), and the median OS was 10.5 months(95% CI, 8.6–12.4). Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months(95% CI, 4.4–5.2), and the median OS was 7.5 months(95% CI, 6.8–8.2). Both PFS and OS showed a statistical difference between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.     

Response rate as an endpoint for evaluating new cytotoxic agents in phase II trials of non-small-cell lung cancer

Background: Response rate (RR) has been used as a defining endpoint of new-agent phase II trials for non-small-cell lung cancer (NSCLC). However, tumor responses to chemotherapy do not always result in prolonged survival of patients with this disease.Design: Single-agent phase II trials were identified by a MEDLINE search of the period from 1976 to 1995. Associations between RR, median survival time (MST) and characteristics of patients who entered the trial, including tumor extent, performance status and prior chemotherapy, were studied by using the logistic regression model.Results: A total of 183 treatment arms in 176 trials (including 10 randomized phase II trials) were identified. The overall RR in the 6768 evaluable patients was 11%. Eleven drugs, cisplatin, epirubicin, ifosfamide, edatrexate, irinotecan, vinorelbine, docetaxel, paclitaxel, etoposide, vindesine, and 254-S, produced a RR of more than 20%. An MST of eight months or longer was obtained with 12 drugs, but there were cases in which no objective responses were produced by these drugs. MST was correlated with RR (r = 0.504, P <; 0.0001), but ranged broadly at a given level of RR. Multiple linear regression analysis showed a significant correlation between RR and MST (regression coefficient = 0.60, P = 0.00003) after adjustment for other variables.Conclusions: RR was significantly correlated with MST in single-agent phase II trials for NSCLC, but there is room for further consideration of the endpoint of these trials.     

Cisplatin and etoposide (VP-16) as a single regimen for small cell lung cancer. A phase II trial

Forty-seven consecutive patients with small cell lung cancer (SCLC) were treated with a combination chemotherapy program including 60 mg/m2 of cisplatin (P) on day 1 and 120 mg/m2 of etoposide (E) on day 4, 6, 8, every 21 days. Limited disease (LD) patients, achieving complete response (CR) or partial response (PR) after the three initial courses, received radiotherapy (RT) to the pretreatment primary tumor volume and, those achieving CR, additional RT to the brain. During RT, chemotherapy was administered with 50% dose reduction. Forty-three patients were evaluable for therapeutic response. In the 19 patients with LD, CR was achieved in 63% of patients and the PR rate was 32%. In 24 patients with extensive disease (ED), CR was 34% and PR rate was 54%. Median duration of survival was 66 weeks for LD and 48 weeks for ED. Six patients were disease-free after 2 years. Leucocyte count less than 2000/mm3 was seen in 26% of patients; platelet count less than 50000/mm3 was observed in 9%. Nonhematologic toxicity included universal nausea or vomiting and severe neurotoxicity in 7%. These data indicate that PE combination is a very active front-line regimen in SCLC and could be suggested as one of the reference treatments.     

Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I-II study

The aim of this study was to evaluate feasibility and toxicity of escalating doses of epirubicin and paclitaxel plus fixed dose of etoposide and to define the activity of the triplet in extensive disease small-cell lung cancer. Thirteen patients entered the phase I study: the maximum tolerated doses were epirubicin (EpiDX) 90 mg m-2 and paclitaxel (P) 175 mg m-2 with febrile neutropenia as dose-limiting toxicity. The recommended schedule for this regimen for the phase II study was EpiDX 75 mg m-2, P 175 mg m-2, etoposide (E) 100 mg m-2 intravenous (fixed dose) days 1-3 with courses repeated every 21 days. The prophylactic use of colony-stimulating factors (CSFs) was not allowed. Twenty patients entered the phase II trial: median age was 61 years (range 50-70), median Eastern Cooperative Oncology Group performance status 0 (0-2); nine patients had visceral disease and 17 had more than two metastatic sites. A total of 100 courses were administered with a median of 5 (range 1-6) per patients. Main toxicity (NCI-CTC) was myelosuppression: neutropenia grades 3 and 4 in 16 and 35% of the courses, respectively. Seven episodes of febrile neutropenia were documented and one patient required hospital admission. Nonhaematological toxicity was moderate. Seven out of 19 evaluable patients achieved a complete response (37%), nine patients (47.3%) a partial response with an overall response rate of 84.2% (95% confidence interval=60.4-96.6). In this poor prognostic population of patients the triplet epirubicin/paclitaxel/etoposide showed high antitumour activity with mild nonhaematological side effects. The use of CSFs should be able to improve the haematological profile.     

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.     

Concurrent cisplatin/etoposide chemotherapy plus twice daily thoracic radiotherapy in limited stage small cell lung cancer: a phase II study

Thirty-one previously untreated patients with limited stage small-cell lung cancer (LSCLC) were included in a prospective study, to investigate the feasability and the efficacy of a combined modality treatment using concurrent hyperfractionated chest irradiation and cisplatin (P) plus etoposide (E) chemotherapy. All patients received intravenously P=75 mg/m(2) at day 1, plus E=120 mg/m(2) days 1-3, at 3-week intervals for six cycles. Irradiated patients received 45 Gy in two daily fractions, 5 days a week, from week 4 to week 6. During week 5, prophylactic cranial irradiation was initiated, in one daily fraction of 2.5 Gy for a total dose of 25 Gy. Twenty-nine patients were evaluable for response. Twenty-two (76%) achieved a complete response, five (17%) had a partial response. Five patients are currently alive. The overall response rate was 93% (CI 95% (83.7-100)). The median survival time was 14 months and the 2-year survival rate was 25%. Main toxicities were grade 3-4 esophagitis in half of the patients and myelosuppression. The results are not as optimistic as other studies using a similar regimen.     

A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer.

A total of 92 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5) (PE) or cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5)/ifosfamide (2 g/m2, days 1, 2, 3) (PEI) combination chemotherapy. After 2 courses of chemotherapy, patients with limited disease (LD) received chest irradiation of 40-50 Gy. Of the 89 patients who could be wholly evaluated, the overall response rate was 78% for PE and 74% for PEI therapy (NS). For all patients the complete response (CR) rates were 14 versus 21%, respectively, and 22 versus 30% for LD. However, the median survival times for all patients were 55 weeks for PE therapy versus 56 weeks for PEI therapy (NS). The 2-year survival rates were 15 and 17%, respectively, for all patients (NS). There was no difference in the duration of response between PE and PEI therapy in cases with CR or partial response. However, severe leukopenia (< 2,000/mm3) occurred more often after PEI (73%) than after PE (44%) therapy (p < 0.05). These results suggest that PEI is not superior to PE chemotherapy in SCLC. The use of ifosfamide in multimodality treatment regimens needs to be studied further.