Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer

Naka, Nobuyuki; Kawahara, Mutsuto; Okishio, Kyoichi; Hosoe, Shigeto; Ogawara, Mitsumasa; Atagi, Shinji; Takemoto, Y; Ueno, Kiyonobu; Kawaguchi, Tomoya; Tsuchiyama, Tessei; Furuse, Kiyoyuki

doi:10.1016/s0169-5002(02)00073-9

Cited by 47 publications

(46 citation statements)

References 12 publications

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“…The combinations of irinotecan with etoposide [19]or carboplatin [20]have been tested in relapsing patients with SCLC. In these trials, response rates as high as 71% (95% CI 53–89) [19]and 31% (95% CI 15–50) [20]have been recorded.…”

Section: Discussionmentioning

confidence: 99%

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A Multicenter Phase II Study of the Combination of Irinotecan and Gemcitabine in Previously Treated Patients with Small-Cell Lung Cancer

et al. 2004

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Objective: To evaluate efficacy and toxicity of the combination of irinotecan and gemcitabine in pretreated patients having small-cell lung cancer. Patients andMethods: Thirty-one patients (median age 60 years, performance status 0–1 in 87% and 2 in 13% of the patients) with limited or extensive-stage disease, refractory or relapsing after at least one prior chemotherapy regimen, received gemcitabine 1,000 mg/m² on days 1 and 8 and irinotecan 300 mg/m² on day 8, every 21 days. Sixteen (52%) patients had sensitive and 15 (48%) refractory disease. Fifteen patients (48%) had received ≧2 prior regimens. Results: All patients were evaluable for toxicity and 26 for response analysis. A median of three (range 1–6) cycles per patient was administered. Three partial responses were documented for an overall response rate of 10% (95% CI 0.73–20.09), and disease stabilization was obtained in 7 patients (22%; intention-to-treat analysis). Two of the responders had refractory, and 1 had sensitive disease. The median time to progression was 4.5 months, the median duration of responses was 2.5 months, and the median survival time was 6 months. Grade 3–4 (WHO) neutropenia was observed in 9 patients (29%), grade 3–4 thrombocytopenia in 4 (13%), and grade 3–4 diahrrea in 3 patients (10%). Three patients experienced febrile neutropenia. No toxic deaths occurred. Conclusions: The combination showed modest activity in this patient group with a poor prognosis. Thus we believe it merits further investigation in the treatment of patients with small-cell lung cancer who have failed one prior chemotherapy regimen.

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Section: Discussionmentioning

confidence: 99%

“…In these trials, response rates as high as 71% (95% CI 53–89) [19]and 31% (95% CI 15–50) [20]have been recorded. Patient selection may also account for the difference in efficacy observed between these trials and ours.…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Phase II Study of the Combination of Irinotecan and Gemcitabine in Previously Treated Patients with Small-Cell Lung Cancer

et al. 2004

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“…All reported response rates have widely overlapping confidence intervals. In addition to the report demonstrating that the combination of cisplatin and irinotecan is highly effective in first-line treatment of SCLC and might improve survival [4], another study demonstrates that irinotecan plus carboplatin is highly effective as second-line treatment in refractory or relapsed SCLC [14]. This group reported a response rate of 23% in patients who had been refractory to first-line therapy and of 38% in patients, who relapsed >90 days after completion of first-line treatment, which is more encouraging than reports on any other drug in primary refractory SCLC.…”

Section: Discussionmentioning

confidence: 97%

Phase I Dose Escalation Study of Carboplatin to a Fixed Dose of Irinotecan as First-Line Treatment of Small Cell Lung Cancer

Schmittel

Schulze²,

Hütter³

et al. 2004

Oncol Res Treat

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Background: Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This study determines dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of escalating doses of carboplatin to a fixed dose of irinotecan in Caucasians with small cell lung cancer. Patients and Methods: Patients with extensive small cell lung cancer received 50 mg/m² irinotecan on day 1, 8, and 15. Dose escalation of carboplatin on day 1 started in dose level 1 at an AUC of 5 mg × min/ml and was escalated to AUC 6 in level 2. Cycles were repeated on day 29. Dose escalation was evaluated after 3 consecutive patients. If no grade IV neutropenia lasting for ≧7 days or thrombopenia or non-hematologic toxicity ≧ grade III occurred, treatment was continued in the next dose level. Results: 16 patients were treated. DLT was reached in dose level 2 with 2 grade IV neutropenias and 1 grade IV thrombopenia and diarrhea. Toxicity was further investigated at dose level 1 in a total of 10 patients, which revealed 2 grade III neutropenias and 1 grade III diarrhea. Of 15 evaluable patients, 10 had a partial response, 3 had disease stabilization and 2 progressed. Conclusion: Dose level 1 was found to be MTD, this dose is currently compared to the combination of etoposide plus carboplatin within a randomised phase II/III trial.

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“…Topotecan is the only chemotherapeutic agent been approved by the FDA for use in the second line setting, and is associated with a median survival of 7 months. [20][21][22] Here, IPM was relatively well tolerated with comparable Grade 3 and 4 myelosuppression compared with the irinotecan and carboplatin, 15 despite the relatively higher irinotecan dose density per cycle (200 mg/m 2 for IPM compared with 150 mg/m 2 ) and despite the addition of mitomycin. Furthermore, IPM was not associated with significant worsening of quality of life as measured by the RCSL.…”

mentioning

confidence: 93%

“…IPM exhibited higher response, PFS and OS compared with irinotecan and carboplatin. 15 There exists a paucity of effective therapy for SCLC in the second line setting, with no satisfactory standard. [16][17][18][19] Where systemic therapy has been used in the second-line setting, there exists evidence to support improved symptom control and survival.…”

mentioning

confidence: 99%

Phase II trial of irinotecan, cisplatin and mitomycin for relapsed small cell lung cancer

Fennell

Steele

Shamash

et al. 2007

Intl Journal of Cancer

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There is no standard therapy for relapsed small cell lung cancer (rSCLC). In order to investigate this further, we evaluated the efficacy and toxicity of a new triplet consisting of irinotecan (100 mg/ m 2 Days 1 and 15 q28), cisplatin (40 mg/m 2 Days 1 and 15 q28) and mitomycin (6 mg/m 2 d1 q28) administered to a maximum of 6 cycles in individuals with rSCLC that had relapsed following first line treatment. Partial remisions were observed in 35% and progression in 30% of patients. Progression free survival measured 4.5 months (95% CI 0.8-8.2) and overall survival was 7.8 months (95% CI 5.3-10.3). QoL showed improvement in activity symptoms and stabilization of physical symptoms. As IPM was a well-tolerated regimen with activity in rSCLC, a phase III trial comparing this triplet with other regimens in this setting is warranted. ' 2007 Wiley-Liss, Inc.Key words: small cell lung cancer; relapsed; triplet; second-line; phase II clinical trial; irinotecan; cisplatin; mitomycin Small cell lung cancer (SCLC) is a rapidly fatal malignancy that accounts for 15% of patients with lung cancer and is characterized by initial chemosensitivity including complete remission (CR) rates as high as 60% in patients with limited disease. Despite this initial high response, patients commonly relapse, and the overall survival (OS) at 5 years for all stages is only 2-5%. 1,2 At relapse, second line response rates are generally lower than those observed first line, and the optimal second line regimen is not yet clear 3,4 although topotecan is superior to best supportive care. 5 The biological basis of this dramatic phenotypic transformation has not been elucidated but may result from acquisition of apoptosis resistance or selection of apoptosis resistant clones. 6 The novel doublet irinotecan and cisplatin have been shown to be effective in a Japanese SCLC series in the first-line setting with an efficacy comparable to etoposide/cisplatin, 7 findings that require clarification in a Western population. However, a phase III trial showed no benefit or irinotecan/cisplatin over etoposide/cisplatin. 8 As mitomycin-C has a long history of use in various histological types of lung cancer, and our recent data has shown its use in mesothelioma, 9 we report the efficacy of the novel triplet irinotecan, cisplatin and mitomycin (IPM) in the second-line SCLC setting.We enrolled 21 patients with histologically confirmed rSCLC and a median age of 51 years (range 37-56) to receive (patients) outpatient irinotecan 100 mg/m 2 , cisplatin 40 mg/m 2 Day 1 and 15, with mitomycin-C at a dose of 6 mg/m 2 administered Day 1 of a 28 day cycle. Mitomycin was omitted after four complete cycles due to known issues with myelosuppression.

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Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer

Cited by 47 publications

References 12 publications

A Multicenter Phase II Study of the Combination of Irinotecan and Gemcitabine in Previously Treated Patients with Small-Cell Lung Cancer

A Multicenter Phase II Study of the Combination of Irinotecan and Gemcitabine in Previously Treated Patients with Small-Cell Lung Cancer

Phase I Dose Escalation Study of Carboplatin to a Fixed Dose of Irinotecan as First-Line Treatment of Small Cell Lung Cancer

Phase II trial of irinotecan, cisplatin and mitomycin for relapsed small cell lung cancer

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