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Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer
154
Abslracts/L.tmg
Cancer
of43 responsesnoted( 16%). Thus, tbetoxiceffectsofthechemotherapy in addition to the inconvenience of hospital visits renders it questionable whether it is worthwhile to continue treatment in patients with inoperable non-small-cell lung cancer beyond day 84 in the absence of response.
TWO schedules of teniposide with or without cisplatin in advanced non- small-cell lung cancer: A randomized Study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Splinter TAW, Sahmoud T, F&en J, Van Zandwijk N, Sorenson S, Clerico M et al. Medical Oncology. Free Vtdversity Hospital, 1117De Boelelaan. HV 1081 Amsterdam. J Clin Oncol 1996; 14: 127-34. Purpose: We conducted a randomized trial to investigate the value of the addition of cisplatin to teniposide (VM26) and to investigate the schedule dependence of the topoisomerase II inhibitor VM26, in advanced non-small- cell lung cancer (NSCLC) patients. Patients and Methoak Two hundred twenty- five NSCLC patients were randomized to receive VM26 120 mg/m’ on days I, 3, and 5 or 360 mglm’ on day 1 only. either as a single drug or in combination with cisplatin 80 mgl m2 on day 1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. Results: The response rate of the two cisplatincontaining arms was superior to that of the hvo arms that contained VM26 only (22% v 646, P < ,001); progression-free survival and survival timeswerealso longerinthecisplatin-containingarms(median, 4.3 v 2.2 months, P = ,003; median 7.2 Y 5.9 months, P = .008. respectively). Toxicitywassignitictly higher in thecisplatin-containing arms; the most frequent side effects were leukopenia, nausea and vomiting, and alopecia. The schedule of VM26 did not significantly influence the response rate, progression-free suIvivaI interval, or survivalduration. However, theresponse rateofthe I-day administration was significantly lower than that of the 3day administration when given as single drugs. Conclusion: The addition of cisplatin to VM26 improves the response rate, progression-free survival interval, and survival duration over VM26 alone, although at the cost of a significant increase in toxicity. Cisplatin should be considered as the basis for combination chemotherapies in advanced NSCLC.
Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensivestage small-cell lung cancer: A North Central Cancer Treatment Group Study Rowland KM Jr, Loprinzi CL, Shaw EG, Maksymiuk AW, Kuross SA, Jung S-H et al. Mayo Clinic, 2# First St SW, Rochester, MN 55905. J Clin Oncol 1996;14:135-41. Purpose: Megestrol acetate has been reported to Improve appetite and quality of life and to decrease nausea and vomiting in patients with cancer anorexialcachexia. The present trial was formulated to evaluate the impact of megestrol acetate onquality of life, toxicity, response, and survival in individuals with extensive-stage small-cell lung cancer who received concomitant chemotherapy. Patients and Methods: Patients were randomized to receive megestrol acetate 800 mg/d orally or placebo. In addition, all patients were scheduled to receive a maximum of four cycles of cisplatin and etoposide chemotherapy. Quality of life was self-assessed at entry onto study, with every cycle of chemotherapy, and 4 months thereafter with a linear visual analog scale. Toxicity was evaluated by patient questionnaire and investigator reports. Results: A total of 243 eligible patients were random&d. Those who received megestrol acetate had increased nonfluid weight gain (P = .004) and signiticantly less nausea (P = .0002) and vomiting (P = .OZ).
I5 (19%)
139-157
Significant thromboembolic phenomena occurred more often in patients who received megestrol acetate versus placebo (9% v 2%. P = .Ol). Patients who received megestrol acetate had more edema (30 96 v 20 96, P = ,002). an inferior response rate to chemotherapy (68 % v 80%. P = .03), and a trend for inferior survival duration (median, 8.2 v 10.0 months, P = .49). These findings may have been influenced by a poorer quality of life of the megestrol acetate group at study initiation. There were no significant changes in quality of life scores over time between either of the study arms. Conclusion: Megestrol acetate cannot be routinely recommended for all patients with small-cell lung cancer at the time of chemotherapy initiation. Rather, its therapeutic ratio may be more favorable for patients with problematic cancer anorexialcachexia.
Phase II trial of a J-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer Millward MJ, Bishop JF, Friedlander M, Levi JA, Goldstein D, Olver IN et al. Div. of Hematology/Medical Oncology, Peter MacCallum Cancer Institute. A’Beckett St, Melbourne 3aK). J Clin Oncol 1996; 14: 142-8. Purpose: To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Fifty-one patientswithadvancedmeasurableorassessableNSCLCandperfotmance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mglm* over 3 hours with premeditation. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57 %), extrathoracic me&static disease (65 W), and measurabledisease(754b). Twenty-two percent hadpreviouslyuntreated stage III disease. Results: The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organiuction (WHO) grade IV neutropenia in only 16 96 of patients. Grade Ill/IV myalgialarthralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. Conclusion: The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase 11 trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.
Clinical pharmacology of chronic oral etoposide in patients with small cell and non-small cell lung cancer Zucchetti M, Pagani 0, Torri V, Sew C, D’lncalci M, De Fusco M et al. Division of Oncology, Ospedale San Giovanni, CH45WBellinzona. Clin Cant Res 1995;1:1517-24. We aimed to evaluate the pharmacokinetics and pharmacodynamics of etoposide given chronically by the p.o. route to patients with small cell and non-small cell lung cancer. Single daily p.o. doses of 100 mg etoposide were given for 21 consecutive days every 4 weeks to 39 previously untreated patients with small cell lung cancer and 10 patients with non-small cell lung cancer. Bioavailability was studied after one i.v. and onep.o. doseof 100 mg etoposide given 48 h beforeand on day 1 of treatment, respectively. Etoposide plasma levels were measured using the HPLC method. Inter- and intrapatient variability of the area under the curve of the concentration versus time (AUC) during the first cycle were evaluated using a limited sampling model; the variability of etoposide plasma concentration (Ecs) during the first cycle was assessed by weekly blood samples taken 24 h after dosing. The overall
Abslracts/L.tmg
Cancer
of43 responsesnoted( 16%). Thus, tbetoxiceffectsofthechemotherapy in addition to the inconvenience of hospital visits renders it questionable whether it is worthwhile to continue treatment in patients with inoperable non-small-cell lung cancer beyond day 84 in the absence of response.
TWO schedules of teniposide with or without cisplatin in advanced non- small-cell lung cancer: A randomized Study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Splinter TAW, Sahmoud T, F&en J, Van Zandwijk N, Sorenson S, Clerico M et al. Medical Oncology. Free Vtdversity Hospital, 1117De Boelelaan. HV 1081 Amsterdam. J Clin Oncol 1996; 14: 127-34. Purpose: We conducted a randomized trial to investigate the value of the addition of cisplatin to teniposide (VM26) and to investigate the schedule dependence of the topoisomerase II inhibitor VM26, in advanced non-small- cell lung cancer (NSCLC) patients. Patients and Methoak Two hundred twenty- five NSCLC patients were randomized to receive VM26 120 mg/m’ on days I, 3, and 5 or 360 mglm’ on day 1 only. either as a single drug or in combination with cisplatin 80 mgl m2 on day 1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. Results: The response rate of the two cisplatincontaining arms was superior to that of the hvo arms that contained VM26 only (22% v 646, P < ,001); progression-free survival and survival timeswerealso longerinthecisplatin-containingarms(median, 4.3 v 2.2 months, P = ,003; median 7.2 Y 5.9 months, P = .008. respectively). Toxicitywassignitictly higher in thecisplatin-containing arms; the most frequent side effects were leukopenia, nausea and vomiting, and alopecia. The schedule of VM26 did not significantly influence the response rate, progression-free suIvivaI interval, or survivalduration. However, theresponse rateofthe I-day administration was significantly lower than that of the 3day administration when given as single drugs. Conclusion: The addition of cisplatin to VM26 improves the response rate, progression-free survival interval, and survival duration over VM26 alone, although at the cost of a significant increase in toxicity. Cisplatin should be considered as the basis for combination chemotherapies in advanced NSCLC.
Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensivestage small-cell lung cancer: A North Central Cancer Treatment Group Study Rowland KM Jr, Loprinzi CL, Shaw EG, Maksymiuk AW, Kuross SA, Jung S-H et al. Mayo Clinic, 2# First St SW, Rochester, MN 55905. J Clin Oncol 1996;14:135-41. Purpose: Megestrol acetate has been reported to Improve appetite and quality of life and to decrease nausea and vomiting in patients with cancer anorexialcachexia. The present trial was formulated to evaluate the impact of megestrol acetate onquality of life, toxicity, response, and survival in individuals with extensive-stage small-cell lung cancer who received concomitant chemotherapy. Patients and Methods: Patients were randomized to receive megestrol acetate 800 mg/d orally or placebo. In addition, all patients were scheduled to receive a maximum of four cycles of cisplatin and etoposide chemotherapy. Quality of life was self-assessed at entry onto study, with every cycle of chemotherapy, and 4 months thereafter with a linear visual analog scale. Toxicity was evaluated by patient questionnaire and investigator reports. Results: A total of 243 eligible patients were random&d. Those who received megestrol acetate had increased nonfluid weight gain (P = .004) and signiticantly less nausea (P = .0002) and vomiting (P = .OZ).
I5 (19%)
139-157
Significant thromboembolic phenomena occurred more often in patients who received megestrol acetate versus placebo (9% v 2%. P = .Ol). Patients who received megestrol acetate had more edema (30 96 v 20 96, P = ,002). an inferior response rate to chemotherapy (68 % v 80%. P = .03), and a trend for inferior survival duration (median, 8.2 v 10.0 months, P = .49). These findings may have been influenced by a poorer quality of life of the megestrol acetate group at study initiation. There were no significant changes in quality of life scores over time between either of the study arms. Conclusion: Megestrol acetate cannot be routinely recommended for all patients with small-cell lung cancer at the time of chemotherapy initiation. Rather, its therapeutic ratio may be more favorable for patients with problematic cancer anorexialcachexia.
Phase II trial of a J-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer Millward MJ, Bishop JF, Friedlander M, Levi JA, Goldstein D, Olver IN et al. Div. of Hematology/Medical Oncology, Peter MacCallum Cancer Institute. A’Beckett St, Melbourne 3aK). J Clin Oncol 1996; 14: 142-8. Purpose: To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Fifty-one patientswithadvancedmeasurableorassessableNSCLCandperfotmance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mglm* over 3 hours with premeditation. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57 %), extrathoracic me&static disease (65 W), and measurabledisease(754b). Twenty-two percent hadpreviouslyuntreated stage III disease. Results: The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organiuction (WHO) grade IV neutropenia in only 16 96 of patients. Grade Ill/IV myalgialarthralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. Conclusion: The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase 11 trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.
Clinical pharmacology of chronic oral etoposide in patients with small cell and non-small cell lung cancer Zucchetti M, Pagani 0, Torri V, Sew C, D’lncalci M, De Fusco M et al. Division of Oncology, Ospedale San Giovanni, CH45WBellinzona. Clin Cant Res 1995;1:1517-24. We aimed to evaluate the pharmacokinetics and pharmacodynamics of etoposide given chronically by the p.o. route to patients with small cell and non-small cell lung cancer. Single daily p.o. doses of 100 mg etoposide were given for 21 consecutive days every 4 weeks to 39 previously untreated patients with small cell lung cancer and 10 patients with non-small cell lung cancer. Bioavailability was studied after one i.v. and onep.o. doseof 100 mg etoposide given 48 h beforeand on day 1 of treatment, respectively. Etoposide plasma levels were measured using the HPLC method. Inter- and intrapatient variability of the area under the curve of the concentration versus time (AUC) during the first cycle were evaluated using a limited sampling model; the variability of etoposide plasma concentration (Ecs) during the first cycle was assessed by weekly blood samples taken 24 h after dosing. The overall