卡铂、异环磷酰胺、依托泊苷和长春新碱联合非格司亭用于小细胞肺癌患者的剂量强度Ⅰ/Ⅱ期试验

Dose intensity phase I/II trial with carboplatin, ifosfamide, etoposide and vincristine combined with filgrastim in patients with small-cell lung cancer.

作者信息

Hanauske A R, Korfel A, Perker M, Heinrich B, Schwab G, Graf M, Depenbrock H, Höffken G, Kreuser E D, Thiel E, Zwingers T, Berdel W E

机构信息

Klinikum rechts der Isar der Technischen Universität München, Germany.

出版信息

Oncology. 1997 Sep-Oct;54(5):363-70. doi: 10.1159/000227719.

DOI:10.1159/000227719

PMID:9260596

Abstract

BACKGROUND

The purpose of the study was to evaluate the feasibility of increasing dose intensity by a stepwise reduction of the time intervals between chemotherapy cycles in separate patient cohorts with small-cell lung cancer. Patients received up to 6 courses of combination chemotherapy with carboplatin, etoposide, ifosfamide and vincristine followed by support with filgrastim. Dose intensity, incidence, duration and severity of neutropenic fever and infections, objective response to chemotherapy, and safety of filgrastim were determined.

PATIENTS AND METHODS

29 patients with small-cell lung cancer (limited disease: 2, extensive disease: 27) were treated with a combination of carboplatin 250 mg/m2 i.v. day 1, ifosfamide 2 g/m2 and etoposide 120 mg/m2 i.v. days 1 and 2, etoposide 120 mg/m2 orally day 3, and vincristine 1.4 mg/m2 day 14. Initially, filgrastim (5 micrograms/kg) was administered subcutaneously from day 7 to 16. With shorter treatment intervals, filgrastim was administered on days 4-16 or 4-14.

RESULTS

An overall increase in dose intensity by a factor of 1.44 was achieved after reducing the treatment interval from 27 to 17 days. Further reduction to 14 days was not feasible due to persistent thrombocytopenia. Six patients (21%) developed a total of 9 febrile episodes, and 14 patients (48%) had to be withdrawn from the study before the completion of six cycles of chemotherapy. The median duration of infectious episodes was 6 days. Overall, a total of 22 of 27 evaluable patients had an objective response. Longer treatment intervals resulted in a lower probability for objective response (> or = 23 days: 10/14 patients vs. < or = 17 days: 7/7 patients).

CONCLUSION

Filgrastim allows for the reduction of treatment intervals in patients with small-cell lung cancer and increased dose intensity with acceptable hematologic and nonhematologic toxicities.

摘要

背景

本研究的目的是评估在小细胞肺癌患者不同队列中，通过逐步缩短化疗周期之间的时间间隔来增加剂量强度的可行性。患者接受多达6个疗程的卡铂、依托泊苷、异环磷酰胺和长春新碱联合化疗，随后给予非格司亭支持治疗。测定剂量强度、中性粒细胞减少性发热和感染的发生率、持续时间及严重程度、化疗的客观缓解率以及非格司亭的安全性。

患者与方法

29例小细胞肺癌患者（局限性疾病：2例，广泛性疾病：27例）接受了卡铂250mg/m²静脉滴注第1天、异环磷酰胺2g/m²和依托泊苷120mg/m²静脉滴注第1天和第2天、依托泊苷120mg/m²口服第3天以及长春新碱1.4mg/m²第14天的联合治疗。最初，非格司亭（5μg/kg）从第7天至第16天皮下注射。随着治疗间隔缩短，非格司亭在第4 - 16天或第4 - 14天给药。

结果

将治疗间隔从27天缩短至17天后，剂量强度总体增加了1.44倍。由于持续的血小板减少，进一步缩短至14天不可行。6例患者（21%）共发生9次发热发作，14例患者（48%）在完成6个化疗周期前不得不退出研究。感染发作的中位持续时间为6天。总体而言，27例可评估患者中有22例有客观缓解。较长的治疗间隔导致客观缓解的概率较低（≥23天：10/14例患者 vs. ≤17天：7/7例患者）。