Havemann K, Wolf M, Holle R, Gropp C, Drings P, Manke H G, Hans K, Schroeder M, Heim M, Victor N
Cancer. 1987 Mar 15;59(6):1072-82. doi: 10.1002/1097-0142(19870315)59:6<1072::aid-cncr2820590605>3.0.co;2-w.
A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.
总共306例小细胞肺癌（SCLC）患者被随机分组，接受序贯或交替模式的化疗。序贯化疗由八个周期的环磷酰胺、阿霉素（多柔比星）和长春新碱（CAV）组成，交替化疗由三个周期（第1、3、5周期）的依托泊苷、长春地辛和异环磷酰胺（EVI）；三个周期（第2、4、6周期）的顺铂、阿霉素和长春新碱（PAV）；以及两个周期（第7、8周期）的环磷酰胺、甲氨蝶呤和洛莫司汀（CMC）组成。有反应的患者在三个周期后接受预防性颅脑照射，化疗八个周期后接受胸部照射。达到完全缓解的患者不进行维持治疗。最短随访时间为2年。在可评估的302例患者中，序贯治疗组的总缓解率为59%，交替治疗组为70%。接受CAV治疗的患者完全缓解率为21%，而接受交替治疗的患者为36%。所有患者的中位生存期分别为9.8个月和11.3个月，局限性疾病患者分别为11.1个月和13.4个月，广泛性疾病患者分别为8.9个月和9.9个月，均显示交替治疗更具优势。所有患者的两年生存率分别为6%和9%，局限性疾病患者分别为11%和14%，广泛性疾病患者分别为3%和6%，均倾向于交替治疗模式。无进展生存期与缓解程度密切相关，与所应用的治疗方案无关。毒性反应包括11例致命和8例危及生命的并发症，交替治疗组的发生率更高。这些结果表明，用不同药物组合交替治疗SCLC比序贯应用CAV更有效。
