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Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer
Abstracts/Lung
Cancer
s&lcell lung ulcer (NSCLC). Patients and Metho&: Docetaxel stage III and IV was administered to 29 patients with tmresdble NSCLC at a dose of 100 mg/m’ intravenously (IV) over I hour every 21 days. No premeditation was given to the first 16 patients. Premeditation with dipknhydramine was instituted for the remainder. No patient had previously received chemotherapy. Seven patients had undergone prior radiation therapy. ResuNs: All patients were assessable for response and toxicity. Eleven of 29 patients (3%) had a major objective response (95% confidence interval, 21% to 58%). The median duration of response was 5.3 months. Febrile neutropenia occurred in 41% of patients and in 11% of 134 courses of docetaxel. Nonhematologic toxicities included infusion-related hypersensitivity readion~, fluid retention, rash, alopecia and sensory kumpamy. Premeditation with dipknhydramine did not decrease the incidence of infusion-related hypersensitivity reactions. Conclusion: At this dose and schedule, &&axe1 demonstrates signiIIcant antitumor activity in patients with a&and NSCLC. Further investigations of this agent in NSCLC are indicated.
A phase II trial of pleurectomyldecorticatioo followed by intrapleural and systemk chemotherapy for malignant pleural mcsotheliema Rusch V, Saltz L, Vkkauaman E, Ginsberg R McCormack P, Burt M et al. Thorocic Service, Department of Surgery, Memorial SioonKettering Cancer Ctr, 1275 York Ave. New York, NY 10021. J Clin Oncol 1994;12:1156-63. Purpose: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesotheliomaby combining surgical resection with immediate postoperative intrapleuml chemotherapy and subsequent systemic chemotherapy. PatientsandMetho& Patients with biopsy- proven, msectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/mg’ and mitomycin 8 mg/m*. Systemic chemotherapy was started 3 to 5 week postoperatively and included cisplatin 50 mg/m* on days 1, 8, 15, 22, 36.43, 50, and 57, and mitomycin 8 mgim’ on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3monthsMtildeathorforaminimumoflSmontbs,whicheveroccurred first. Results: Of36 patients entered onto the study, 28 had pkuectomy/ decortication and intrapleural chemotherapy. There was one pOStoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who al= had systemic chemotherapy nxeived a median of SO?/0and 87% of the planned total cisplatin and mitomycin doses, reqctively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were Originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. L~~~regional disease was the most common form of relapse (16 of 20 patients). Conclusion: This short but aggressive combined modality regimen was generally well tolerated, but should not k used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control. Plaeebo-coatrolled trial of hydraziw sulfate in patients with newly diagnosed non-small-cell lung cancer Loprinzi CL, Goldberg EM. Su JQ, Mailliard JA, Kuross SA, Maksymiuk AW et al. Mayo Clinic, 200 First St SK Rocheste,: MN 55905. J Clin Oncol 1994; 12: 1126-9. Purpose: Hydrazine sulfate, an agent that appears to inhibit ghrconeogenesis, has been studied in cancer patients for approximately
12 (1995)
113-160
153
20 years. There was a recent resurgence of interest in this drug when subset analysis of a small pkebo-controlled, double-blind, clinical trial reported improved survival among non-smallcell lung cancer patients with a good performance status who were randomized to receive this drug along with standard ckmotkrapy. PotientsandMethti Patients on this trial had newly diagnosed, umemcmble non-small-cell lung cancer and were treated with cisplatin and etoposide. In addition, they were randomized to receive hydmzine suEhte or placebo in a doubleblind manner. Results: A total of 243 patients were randomized. Response rates were similar in tk two treatment arms. There were trends for worse time to progression and survival in the hydrazine sulfate arm. No significant ditferences were noted in the two study arms with regard to toxicity or quaky of life (QL). Conclusion: This trial failed to demonstrate any benefit for patients who received hydmziue sulfate.
Cisplatin, vIahlastine, and hydrazine sulfate in advanced, ooo-smallcell lung cancer: A randomized placebo-controlled, double-blind phase Ill study of the cancer and leukemia group B Kosty MP, Fleishman SB, Herndon JE IL Coughlin K, Komblith AB, Scalzo A et al. Hematolo@‘Uedical Oncology. IdaU./Cecil H. Green Cancer Cente,: Scripps Clinic/Research Foundation, 10666 N Torrey PinesRd, Son Diego, CA 92037. J Clin Oncol 1994;12:1113-20. Purpose: To assess the chemotherapy regimen of cisplatin, vinblastine, and hydrazine sulfate adminIstered to patients with non-small-cell lung cancer (NSCLC) in a tandomized, placeboumtroUed double-blind phase III sh@. Patients and Methods: Between July 25.1989 and February 1, 1991,291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m* intravenously (IV) every 28 days, vinblastine 5 mp/mr IV per week times five, then every 2 week; and either hydrazine sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimuknts was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the inthrence of hydrazine s&ate on nutritional status, performance status, and quality of life was also amesmd. Results: Analysis of266 eligible patients showed a median survival duration of 7.78 months for the hydrazine sulfatetreated group compared with 7.70 months for the pkebo-treated group (F = .65, log-rank). Objective response rates were similar for the two groups, with 4% complete responses, 20% partial responses, and 2% regressions in those treated with hydrazine sulfate; 3% complete responses, 23% partial responses, and 2% regressions in those who received placebo. The major toxicity was severe or life-threatening neutropenia, which occurmd in 65% of hydmzine sulfate patients and 63% of placebo patients. There were no differences noted between the two groups in degree of anorexia, weight gain or loss, or overall nutritional status. Sensory and motor neuropathy occurred signiticantly more often in patients treated with hydra&e sulfate. Quaky of life was signifmantiy worse in patients who received hydrazine sulfate. Conclusion: This study suggests no benefit from the addition of hydrazine sulfate to an effective cytotoxic regimen.
Phase I clinical trial of iriaotecan (CPT-ll), ‘I-ethyl-lo-(4-(lpiperidino)-1-piperid~o]ca~nylory-elm, and cisplatia in combination with fixed dose of viadesise in advanced non-small ceil lung cancer Shinkai T, Arioka II, KunIkane II, Eguchi K, Sasshi Y, Tamma T et al. Department of Internal Medicine, Notional Cancer Center Hospital. Tmkvi S-chome. Chuo-ku. Tokyo 104. Cancer Res 1994;54:2636-42. Irinotecan hydrochloride (WI-II), a semisynthetic derivative of camptothecin, has been demonstrated to k active against solid tumors
Cancer
s&lcell lung ulcer (NSCLC). Patients and Metho&: Docetaxel stage III and IV was administered to 29 patients with tmresdble NSCLC at a dose of 100 mg/m’ intravenously (IV) over I hour every 21 days. No premeditation was given to the first 16 patients. Premeditation with dipknhydramine was instituted for the remainder. No patient had previously received chemotherapy. Seven patients had undergone prior radiation therapy. ResuNs: All patients were assessable for response and toxicity. Eleven of 29 patients (3%) had a major objective response (95% confidence interval, 21% to 58%). The median duration of response was 5.3 months. Febrile neutropenia occurred in 41% of patients and in 11% of 134 courses of docetaxel. Nonhematologic toxicities included infusion-related hypersensitivity readion~, fluid retention, rash, alopecia and sensory kumpamy. Premeditation with dipknhydramine did not decrease the incidence of infusion-related hypersensitivity reactions. Conclusion: At this dose and schedule, &&axe1 demonstrates signiIIcant antitumor activity in patients with a&and NSCLC. Further investigations of this agent in NSCLC are indicated.
A phase II trial of pleurectomyldecorticatioo followed by intrapleural and systemk chemotherapy for malignant pleural mcsotheliema Rusch V, Saltz L, Vkkauaman E, Ginsberg R McCormack P, Burt M et al. Thorocic Service, Department of Surgery, Memorial SioonKettering Cancer Ctr, 1275 York Ave. New York, NY 10021. J Clin Oncol 1994;12:1156-63. Purpose: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesotheliomaby combining surgical resection with immediate postoperative intrapleuml chemotherapy and subsequent systemic chemotherapy. PatientsandMetho& Patients with biopsy- proven, msectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/mg’ and mitomycin 8 mg/m*. Systemic chemotherapy was started 3 to 5 week postoperatively and included cisplatin 50 mg/m* on days 1, 8, 15, 22, 36.43, 50, and 57, and mitomycin 8 mgim’ on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3monthsMtildeathorforaminimumoflSmontbs,whicheveroccurred first. Results: Of36 patients entered onto the study, 28 had pkuectomy/ decortication and intrapleural chemotherapy. There was one pOStoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who al= had systemic chemotherapy nxeived a median of SO?/0and 87% of the planned total cisplatin and mitomycin doses, reqctively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were Originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. L~~~regional disease was the most common form of relapse (16 of 20 patients). Conclusion: This short but aggressive combined modality regimen was generally well tolerated, but should not k used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control. Plaeebo-coatrolled trial of hydraziw sulfate in patients with newly diagnosed non-small-cell lung cancer Loprinzi CL, Goldberg EM. Su JQ, Mailliard JA, Kuross SA, Maksymiuk AW et al. Mayo Clinic, 200 First St SK Rocheste,: MN 55905. J Clin Oncol 1994; 12: 1126-9. Purpose: Hydrazine sulfate, an agent that appears to inhibit ghrconeogenesis, has been studied in cancer patients for approximately
12 (1995)
113-160
153
20 years. There was a recent resurgence of interest in this drug when subset analysis of a small pkebo-controlled, double-blind, clinical trial reported improved survival among non-smallcell lung cancer patients with a good performance status who were randomized to receive this drug along with standard ckmotkrapy. PotientsandMethti Patients on this trial had newly diagnosed, umemcmble non-small-cell lung cancer and were treated with cisplatin and etoposide. In addition, they were randomized to receive hydmzine suEhte or placebo in a doubleblind manner. Results: A total of 243 patients were randomized. Response rates were similar in tk two treatment arms. There were trends for worse time to progression and survival in the hydrazine sulfate arm. No significant ditferences were noted in the two study arms with regard to toxicity or quaky of life (QL). Conclusion: This trial failed to demonstrate any benefit for patients who received hydmziue sulfate.
Cisplatin, vIahlastine, and hydrazine sulfate in advanced, ooo-smallcell lung cancer: A randomized placebo-controlled, double-blind phase Ill study of the cancer and leukemia group B Kosty MP, Fleishman SB, Herndon JE IL Coughlin K, Komblith AB, Scalzo A et al. Hematolo@‘Uedical Oncology. IdaU./Cecil H. Green Cancer Cente,: Scripps Clinic/Research Foundation, 10666 N Torrey PinesRd, Son Diego, CA 92037. J Clin Oncol 1994;12:1113-20. Purpose: To assess the chemotherapy regimen of cisplatin, vinblastine, and hydrazine sulfate adminIstered to patients with non-small-cell lung cancer (NSCLC) in a tandomized, placeboumtroUed double-blind phase III sh@. Patients and Methods: Between July 25.1989 and February 1, 1991,291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m* intravenously (IV) every 28 days, vinblastine 5 mp/mr IV per week times five, then every 2 week; and either hydrazine sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimuknts was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the inthrence of hydrazine s&ate on nutritional status, performance status, and quality of life was also amesmd. Results: Analysis of266 eligible patients showed a median survival duration of 7.78 months for the hydrazine sulfatetreated group compared with 7.70 months for the pkebo-treated group (F = .65, log-rank). Objective response rates were similar for the two groups, with 4% complete responses, 20% partial responses, and 2% regressions in those treated with hydrazine sulfate; 3% complete responses, 23% partial responses, and 2% regressions in those who received placebo. The major toxicity was severe or life-threatening neutropenia, which occurmd in 65% of hydmzine sulfate patients and 63% of placebo patients. There were no differences noted between the two groups in degree of anorexia, weight gain or loss, or overall nutritional status. Sensory and motor neuropathy occurred signiticantly more often in patients treated with hydra&e sulfate. Quaky of life was signifmantiy worse in patients who received hydrazine sulfate. Conclusion: This study suggests no benefit from the addition of hydrazine sulfate to an effective cytotoxic regimen.
Phase I clinical trial of iriaotecan (CPT-ll), ‘I-ethyl-lo-(4-(lpiperidino)-1-piperid~o]ca~nylory-elm, and cisplatia in combination with fixed dose of viadesise in advanced non-small ceil lung cancer Shinkai T, Arioka II, KunIkane II, Eguchi K, Sasshi Y, Tamma T et al. Department of Internal Medicine, Notional Cancer Center Hospital. Tmkvi S-chome. Chuo-ku. Tokyo 104. Cancer Res 1994;54:2636-42. Irinotecan hydrochloride (WI-II), a semisynthetic derivative of camptothecin, has been demonstrated to k active against solid tumors