PROSPECTIVE RANDOMIZED COMPARISON OF HIGH-DOSE AND STANDARD-DOSE ETOPOSIDE AND CISPLATIN CHEMOTHERAPY IN PATIENTS WITH EXTENSIVE-STAGE SMALL-CELL LUNG-CANCER

被引:220
|
作者
IHDE, DC
MULSHINE, JL
KRAMER, BS
STEINBERG, SM
LINNOILA, RI
GAZDAR, AF
EDISON, M
PHELPS, RM
LESAR, M
PHARES, JC
GRAYSON, J
MINNA, JD
JOHNSON, BE
机构
[1] NCI, USN, MED ONCOL BRANCH, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA
[2] NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD USA
[3] NATL NAVAL MED CTR, DEPT MED, BETHESDA, MD USA
[4] UNIFORMED SERV UNIV HLTH SCI, DEPT RADIOL, BETHESDA, MD USA
关键词
D O I
10.1200/JCO.1994.12.10.2022
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: We performed a prospective randomized clinical trial to determine whether higher doses of etoposide and cisplatin (EP) yield more complete responses or longer survival in small-cell lung cancer (SCLC) patients. Patients and Methods: Ninety patients with previously untreated extensive-stage SCLC: fulfilled criteria for randomization to standard dose versus high-dose EP. Another 25 patients at risk of excessive toxicity from high-dose treatment were given standard-dose therapy. During cycles 1 and 2 of EP, patients on standard-dose treatment received intravenous etoposide 80 mg/m(2) on days 1 to 3 and cisplatin 80 mg/m(2) on day 1 every 3 weeks; high-dose treatment consisted of etoposide 80 mg/m(2) on days 1 to 5 and cisplatin 27 mg/m(2) on days 1 to 5 every 3 weeks. All patients received standard-dose EP in cycles 3 and 4. In cycles 5 through 8, completely responding patients continued standard-dose EP; all other patients received either cyclophosphamide, doxorubicin, and vincristine, or (if possible) a combination drug program based on in vitro drug sensitivity testing of tumor-cell lines established from individual patients. Results: Despite 68% higher doses and a 46% higher dose-rate intensity actually given to patients randomized to receive high-dose relative to chose randomised to receive standard-dose EP, complete response rates (23% v 22%; P = .99) and median survival durations (10.7 and 11.4 months, respectively; P = .68) were virtually identical. Complete responses occurred in 4% of patients and the median survival duration was 5.8 months in nonrandomized patients. Leukopenia (P < .0001), thrombocytopenia (P < .0001), febrile neutropenia (P = .01), and weight loss (P = .02) were significantly more common in patients randomized to receive high-dose compared with standard-dose EP. Conclusion: No therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities.
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页码:2022 / 2034
页数:13
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