PURPOSE: The combination of etoposide (E) and cisplatin (P) is an accepted standard therapy for small-cell lung cancer (SCLC); however, the optimal sequencing and administration schedule has not been defined. This study was designed to evaluate different sequencing and administration schedules of E and P in the treatment of SCLC. PATIENTS AND METHODS: Five hundred fifty-two eligible patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV) bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30 mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P 45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of IV EP were administered 4 weeks apart. Subsequent therapy was the same for all arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) were administered to responders. RESULTS: The overall response rate (84%) was similar in all treatment arms. Treatment arm A was associated with the best complete response (CR) rate (52%), the most favorable median survival time (MST) of 15 months, and a 26% 2-year survival rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival rate. Multivariate analysis indicated that extent of disease, performance status, arm of therapy, and sex were significant independent factors influencing survival. Toxicity of the four regimens was similar, except for greater thrombocytopenia on arm D. CONCLUSION: The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.
RCT Entities:
PURPOSE: The combination of etoposide (E) and cisplatin (P) is an accepted standard therapy for small-cell lung cancer (SCLC); however, the optimal sequencing and administration schedule has not been defined. This study was designed to evaluate different sequencing and administration schedules of E and P in the treatment of SCLC. PATIENTS AND METHODS: Five hundred fifty-two eligible patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV) bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30 mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P 45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of IV EP were administered 4 weeks apart. Subsequent therapy was the same for all arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) were administered to responders. RESULTS: The overall response rate (84%) was similar in all treatment arms. Treatment arm A was associated with the best complete response (CR) rate (52%), the most favorable median survival time (MST) of 15 months, and a 26% 2-year survival rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival rate. Multivariate analysis indicated that extent of disease, performance status, arm of therapy, and sex were significant independent factors influencing survival. Toxicity of the four regimens was similar, except for greater thrombocytopenia on arm D. CONCLUSION: The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.
Authors: Huw D Thomas; David J Porter; Imke Bartelink; Joy R Nobbs; Michael Cole; Suzie Elliott; David R Newell; A Hilary Calvert; Martin Highley; Alan V Boddy Journal: Br J Clin Pharmacol Date: 2002-01 Impact factor: 4.335
Authors: Nathan R Foster; Lindsay A Renfro; Steven E Schild; Mary W Redman; Xiaofei F Wang; Suzanne E Dahlberg; Keyue Ding; Penelope A Bradbury; Suresh S Ramalingam; David R Gandara; Taro Shibata; Nagahiro Saijo; Everett E Vokes; Alex A Adjei; Sumithra J Mandrekar Journal: J Thorac Oncol Date: 2015-07 Impact factor: 15.609
Authors: Nathan R Foster; Yingwei Qi; Qian Shi; James E Krook; John W Kugler; James R Jett; Julian R Molina; Steven E Schild; Alex A Adjei; Sumithra J Mandrekar Journal: Cancer Date: 2010-10-19 Impact factor: 6.860
Authors: Alan H Bryce; Bassam Mattar; Shauna L Hillman; Alex A Adjei; John W Kugler; Kendrith Rowland; Donald B Wender; Gamini Soori; Edith A Perez; James R Jett Journal: Am J Clin Oncol Date: 2010-08 Impact factor: 2.339
Authors: Nathan R Foster; Sumithra J Mandrekar; Steven E Schild; Garth D Nelson; Kendrith M Rowland; Richard L Deming; Timothy F Kozelsky; Randolph S Marks; James R Jett; Alex A Adjei Journal: Cancer Date: 2009-06-15 Impact factor: 6.860
Authors: H Okamoto; K Watanabe; H Kunikane; A Yokoyama; S Kudoh; T Asakawa; T Shibata; H Kunitoh; T Tamura; N Saijo Journal: Br J Cancer Date: 2007-06-19 Impact factor: 7.640