PURPOSE To assess activity and toxicity of topotecan in previously treated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS Patients with measurable SCLC, progressive after one first-line regimen, were eligible for the study. Two groups of patients were selected: (1) patients who failed first-line treatment < or = 3 months from chemotherapy discontinuation (refractory group); and (2) patients who responded to first-line treatment and progressed greater than 3 months after chemotherapy discontinuation (sensitive group). Topotecan was administered as a 30-minute daily infusion at a dose of 1.5 mg/m2 for 5 consecutive days, every 3 weeks. RESULTS One hundred one patients were entered onto the study and 403 courses were administered. Ninety-two patients (47 refractory and 45 sensitive) were eligible and assessable for response. Among refractory patients, there were two partial responses (PRs) and one complete response (CR), for an overall response rate of 6.4% (95% confidence interval [CI], 1.3% to 17.6%), whereas in the sensitive group, there were 11 PRs and six CRs, for an overall response rate of 37.8% (95% CI, 23.8% to 53.5%). Overall median duration of response was 7.6 months. Median survival was 5.4 months; median survival of refractory patients was 4.7 months, whereas that of sensitive patients was 6.9 months (P = .002). Median survival of responding patients was 12.5 months. Toxicity was mainly hematologic. Leukopenia, although short-lived, was universal, with grade III and IV neutropenia occurring in 28% and 46.8% of cycles, respectively. Nonhematological toxicity was mild. Fatigue/malaise was reported in 39.3% of cycles and transient elevation of liver enzymes in 17%. CONCLUSION Topotecan has significant activity in SCLC, particularly in patients sensitive to prior chemotherapy, with predictable and manageable toxicity. The incorporation of topotecan in combination chemotherapy regimens for future treatment of SCLC is warranted.

Purpose: To assess activity and toxicity of topotecon in previously treated small-cell lung cancer (SCLC) patients.Patients and Methods: Patients with measurable SCLC, progressive after one first-line regimen, were eligible for the study. Two groups of patients were selected: (1) patients who failed first-line treatment less than or equal to 3 months from chemotherapy discontinuation (refractory group); and (2) patients who responded to first-line treatment and progressed greater than 3 months after chemotherapy discontinuation (sensitive group). Topotecan was administered as a 30-minute daily infusion at a dose of 1.5 mg/m(2) for 5 consecutive days, every 3 weeks.Results: One hundred one patients were entered onto the study and 403 courses were administered. Ninety-two patients (47 refractory and 45 sensitive) were eligible and assessable for response. Among refractory patients, there were two partial responses (PRs) and one complete response (CR), for an overall response rate of 6.4% (95% confidence interval [CI], 1.3% to 17.6%), whereas in the sensitive group, there were 11 PRs and six CRs, for an overall response rate of 37.8% (95% CI, 23.8% to 53.5%). Overall median duration of response was 7.6 months. Median survival was 5.4 months; median survival of refractory patients was 4.7 months, whereas that of sensitive patients was 6.9 months (P=.002). Median survival of responding patients was 12.5 months. Toxicity was mainly hematologic. Leukopenia, although short-lived, was universal, with grade III and IV neutropenia occurring in 28% and 46.8% of cycles, respectively. Nonhematological toxicity was mild. Fatigue/malaise was reported in 39.3% of cycles and transient elevation of liver enzymes in 17%.Conclusion: Topotecan has significant activity in SCLC, particularly in patients sensitive to prior chemotherapy, with predictable and manageable toxicity. The incorporation of topotecan in combination chemotherapy regimens for future treatment of SCLC is warranted. (C) 1997 by American Society of Clinical Oncology.

In a multicentre trial of the EORTC-Early Clinical Trials Group (ECTG) we treated 31 chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) with rhizoxin, a novel tubulin-binding agent. The drug was given as an i.v. bolus injection at 2 mg m-2 once every 3 weeks in an outpatient setting. Prophylactic antiemetics were not routinely given. Of the 29 eligible patients, nine had been treated surgically and three had received radiotherapy. The main toxic effects observed were stomatitis (34% of cycles) and neutropenia (41% of cycles). Neutropenic fever was rare (3% of cycles). Twenty-seven patients were evaluable for response. There were four partial responses (15%), while 13 patients (48%) showed stabilisation of their disease. The median duration of response was 7 months (range 6.0-10.7 months) and median survival from the start of rhizoxin treatment was 6 months (range 2-14.7 months). Rhizoxin as single agent shows activity in patients with advanced NSCLC.

Topotecan (T) is a semisynthetic-camptothecin analog with specific topoisomerase I inhibitory effect and preclinical activity in a broad range of tumors including SCLC. A multicentre Phase II study to assess activity and toxicity in pretreated SCLC patients (pts) has recently been closed. Two groups of pts were enrolled: “sensitive” (S) pts who responded to 1st line chemotherapy (CT) but progressed <3 months afterwards and “refractory” (R) pts who never responded to 1st line CT or progressed <3 months after 1st line CT. T was administered iv at a dose of I. 5 mg/m2 d×5 q3 weeks until progression or excessive toxicity. A total of 94 eligible pts were entered and 353 courses (crs) and 87 pts (48 R, 39 S) have been evaluated. Pts characteristics are: median age 59, median PS 1, median duration of prior CT 4 months and median No. of prior drugs 3. In 39 S pts 5 CR and 13 PR were observed (46%), in 48 R pts 1 CR and 3 PR (8%). Toxicity (NCI grading) was mainly hematological. Leucopenia, although short lived was common with gr. III and IV neutropenia occurring in 78% of crs. Nine pts developed infections, 2 died while neutropenic. Gr. III and IV thrombocytopenia was observed in 29% of crs and 54% of pts. Anemia gr. III and IV occurred in 29% of pts. Non-hematological toxicity was mild. Asthenia was observed in 35% of crs with only 3 gr. IV episodes. Diarrhea was reported in 12 crs (1 gr. III), vomiting gr. III in only I crs. Toxicity required dose reduction in 10% of courses, treatment delay in 18% of crs. Preliminary results indicate that the concept of testing new drugs in S and R pts is feasible, that T has significant activity, especially in S, but even in R pts, and that toxicity is manageable. The study is closed for patient entry and final results will be available in October 1995. Topotecan (T) is a semisynthetic-camptothecin analog with specific topoisomerase I inhibitory effect and preclinical activity in a broad range of tumors including SCLC. A multicentre Phase II study to assess activity and toxicity in pretreated SCLC patients (pts) has recently been closed. Two groups of pts were enrolled: “sensitive” (S) pts who responded to 1st line chemotherapy (CT) but progressed <3 months afterwards and “refractory” (R) pts who never responded to 1st line CT or progressed <3 months after 1st line CT. T was administered iv at a dose of I. 5 mg/m2 d×5 q3 weeks until progression or excessive toxicity. A total of 94 eligible pts were entered and 353 courses (crs) and 87 pts (48 R, 39 S) have been evaluated. Pts characteristics are: median age 59, median PS 1, median duration of prior CT 4 months and median No. of prior drugs 3. In 39 S pts 5 CR and 13 PR were observed (46%), in 48 R pts 1 CR and 3 PR (8%). Toxicity (NCI grading) was mainly hematological. Leucopenia, although short lived was common with gr. III and IV neutropenia occurring in 78% of crs. Nine pts developed infections, 2 died while neutropenic. Gr. III and IV thrombocytopenia was observed in 29% of crs and 54% of pts. Anemia gr. III and IV occurred in 29% of pts. Non-hematological toxicity was mild. Asthenia was observed in 35% of crs with only 3 gr. IV episodes. Diarrhea was reported in 12 crs (1 gr. III), vomiting gr. III in only I crs. Toxicity required dose reduction in 10% of courses, treatment delay in 18% of crs. Preliminary results indicate that the concept of testing new drugs in S and R pts is feasible, that T has significant activity, especially in S, but even in R pts, and that toxicity is manageable. The study is closed for patient entry and final results will be available in October 1995.

The antitumour activity of docetaxel was investigated in patients with advanced malignant melanoma. Docetaxel, 100 mg/m2, intravenous, over 60 min, was administered every 3 weeks. Response evaluation was performed after two cycles. No prophylactic treatment with steroids or antihistamines was given. 38 patients were included, 36 were eligible and evaluable for toxicity and 30 patients were evaluable for response. The main haematological toxicity was neutropenia [17 patients with common toxicity criteria (CTC) grade 4 and 11 CTC grade 3] with nadir after 5-8 days and rapid recovery. The most frequent non-haematological toxicity was generalised alopecia (83% of the patients). Asthenia, malaise and fatigue were also seen in 58%. Skin toxicity was also frequent. Hypersensitivity reactions (erythematous rash, urticaria, blood pressure changes and tachycardia), seen in 42% of the patients, were mild to moderate. Oedema was registered in one fifth of the patients and developed after four or more treatment cycles. The overall response rate in the evaluable patients was 17% (five partial responders). We conclude that docetaxel has activity in advanced malignant melanoma.

In a multicentre trial of the EORTC ECTG we have treated 43 non-pretreated patients with advanced non-small-cell lung cancer (NSCLC) with the new semisynthetic taxoid docetaxel (Taxotere). Six patients were ineligible; of the 37 eligible patients, ten had prior radiotherapy and 18 prior surgery. They received 100 mg m-2 in 1 h i.v. every 3 weeks, usually in an outpatient setting. Prophylactic steroids, antihistaminics or antiemetics were not routinely given. Two patients were not evaluable because they withdrew from the study because of a hypersensitivity reaction after the second cycle. The main toxicity was neutropenia (80% of cycles), although infections were rare (4%). One patient died from sepsis during neutropenia. Hypersensitivity reactions necessitating interruption of docetaxel (Taxotere) infusions were found in only 10% of cycles. The overall response rate was 23% with one complete response, and seven partial responses. Stable disease was found in 16 patients. The median duration of response was 36 weeks, and the median survival of all patients was 11 months. Docetaxel (Taxotere) is among the most active drugs for treatment of NSCLC.