Fischer J R, Manegold C, Bülzebruck H, Vogt-Moykopf I, Drings P
Department of Medical Oncology, Thoraxklinik Heidelberg-Rohrbach, Germany.
Semin Oncol. 1994 Jun;21(3 Suppl 4):20-7.
Patients with non-small cell lung cancer (NSCLC) in stage IIIA with more than minimal N2 involvement or in stage IIIB are considered unresectable. Response rates to chemotherapy for these patients are in the range of 40%. Reduction of tumor mass by induction chemotherapy may lead to resectability and to improved survival. We evaluated response rates and determined influence of induction chemotherapy on survival when followed by surgery and radiotherapy in 60 patients with primarily inoperable stage IIIA/IIIB NSCLC. The following cytotoxic regimens were used: cisplatin (100 mg/m2) and vindesine (3 mg/m2); ifosfamide (10 g/m2) and etoposide (360 mg/m2); or a combination of cisplatin (75 mg/m2), ifosfamide (6 g/m2), and etoposide (360 mg/m2). Sixty patients were treated with two to four cycles of these regimens between June 1988 and October 1992. In 40 patients chemotherapy was repeated every 4 weeks. In 20 patients chemotherapy was intensified by interval reduction to 3 weeks with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) support. The median patient age was 54 years, and Eastern Cooperative Oncology Group performance status was 0 to 2. Distribution of stages IIIA and IIIB was 21 and 39 in all patients and 5 and 15 in the group treated with r-metHuG-CSF support, respectively. The overall response rate (complete plus partial responses) was 35%. In patients treated with intensified chemotherapy and r-metHuG-CSF support, the response rate was 60%. In 37 patients (61.6%) tumor was resected 4 to 6 weeks after the last cycle of chemotherapy; R0 resection was achieved in 22 patients, R1 in eight patients, and R2 in seven patients. With a follow-up of 4 to 60 months, 1-year survival in patients with tumor regression after chemotherapy and tumor resection was 82.2% versus 35.7% in nonresponders; 2-year survival of responders and nonresponders was 50.9% and 12.8%, respectively; and median survival was 23 months and 9 months, respectively (P < .001). Median survival rates for responders with stage IIIA and IIIB disease were 39 and 17 months, respectively. Median survival after response to chemotherapy and incomplete resection (11 patients) was 17 months, whereas median survival after response to chemotherapy and complete resection (18 patients) has not yet been reached. Only four patients in this group have died with a follow-up of 4 to 60 months. Of 20 patients receiving accelerated chemotherapy with r-metHuG-CSF support, World Health Organization grades 3 and 4 neutropenia occurred in five and eight patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
ⅢA期且N2受累超过轻微程度或ⅢB期的非小细胞肺癌（NSCLC）患者被认为无法切除。这些患者的化疗缓解率在40%左右。诱导化疗使肿瘤肿块缩小可能会导致肿瘤可切除并提高生存率。我们评估了60例最初无法手术的ⅢA/ⅢB期NSCLC患者的缓解率，并确定了诱导化疗继以手术和放疗后对生存的影响。使用了以下细胞毒性方案：顺铂（100mg/m²）和长春地辛（3mg/m²）；异环磷酰胺（10g/m²）和依托泊苷（360mg/m²）；或顺铂（75mg/m²）、异环磷酰胺（6g/m²）和依托泊苷（360mg/m²）的联合方案。1988年6月至1992年10月期间，60例患者接受了两至四个周期的这些方案治疗。40例患者每4周重复进行化疗。20例患者通过将间隔缩短至3周并给予重组人粒细胞集落刺激因子（r-metHuG-CSF，非格司亭）支持来强化化疗。患者中位年龄为54岁，东部肿瘤协作组体能状态为0至2。ⅢA期和ⅢB期在所有患者中的分布分别为21例和39例，在接受r-metHuG-CSF支持治疗的组中分别为5例和15例。总缓解率（完全缓解加部分缓解）为35%。在接受强化化疗和r-metHuG-CSF支持治疗的患者中，缓解率为60%。37例患者（61.6%）在最后一个化疗周期后4至6周进行了肿瘤切除；22例患者实现了R0切除，8例患者为R1切除，7例患者为R2切除。随访4至60个月，化疗后肿瘤缩小并进行肿瘤切除的患者1年生存率为82.2%，而未缓解者为35.7%；缓解者和未缓解者的2年生存率分别为50.9%和12.8%；中位生存期分别为23个月和9个月（P<0.001）。ⅢA期和ⅢB期疾病缓解者的中位生存期分别为39个月和17个月。化疗后缓解但切除不完全的患者（11例）中位生存期为17个月，而化疗后缓解且完全切除的患者（18例）中位生存期尚未达到。该组中仅4例患者在4至60个月的随访期内死亡。在20例接受r-metHuG-CSF支持加速化疗的患者中，世界卫生组织3级和4级中性粒细胞减少分别发生在5例和8例患者中。
