Shepherd F A, Burkes R, Cormier Y, Crump M, Feld R, Strack T
Department of Medicine, Toronto Hospital, Ontario, Canada.
Lung Cancer. 1996 Feb;14(1):135-44. doi: 10.1016/0169-5002(95)00518-8.
A phase I trial was performed to investigate the tolerability and efficacy of the novel nucleoside analogue gemcitabine in combination with cisplatin in the treatment of advanced non-small cell lung cancer. Both cisplatin and gemcitabine were administered as 30 min infusions weekly x 3 with a week of rest. There was one dose escalation of cisplatin from 25 mg/m2 (dose level 1) to 30 mg/m2 (in subsequent dose levels 2-5), such that the mean dose intensity for the weekly x 3 q 4 week cycle was 22.5 mg/m2/week which is close to that achieved with 100 mg/m2 bolus monthly. Gemcitabine was initiated at 1000 mg/m2 (dose levels 1 and 2) then escalated by 250 mg/m2/week to 1750 mg/m2 (dose level 5). Of 32 chemotherapy-naive patients entered (22 males, 10 females; median age 61 years, range 29-74 years), 11 had localized tumours (2 stage IIIa, 9 IIIb) and 21 had stage IV tumours with haematogenous metastases and a poor prognosis. Twenty-one patients had adenocarcinoma, 4 squamous cell carcinoma, 6 large cell undifferentiated tumors, and one had mixed squamous and adenocarcinoma. Dose-limiting toxicity was not seen in more than one patient in cycle 1 at any dose level. Grade 4 granulocytopenia and thrombocytopenia occurred more frequently with repeated dosing, necessitating dose reductions except at the lowest dose level (cisplatin 25 mg/m2, gemcitabine 1000 mg/m2). Non-haematological toxicity was mild and rapidly reversible. Cisplatin administration led to a higher frequency of nausea and vomiting than that seen with gemcitabine alone, but this was easily controlled with antiemetics. In the 28 patients evaluable, to date responses have been seen at most dose levels, with an overall response rate 35.7%. This phase I trial is ongoing and further dose escalation is intended to determine the MTD of gemcitabine.
进行了一项I期试验，以研究新型核苷类似物吉西他滨联合顺铂治疗晚期非小细胞肺癌的耐受性和疗效。顺铂和吉西他滨均每周输注30分钟，共3周，休息1周。顺铂有一次剂量递增，从25mg/m²（剂量水平1）增至30mg/m²（在随后的剂量水平2 - 5），因此每4周一次、每周3次的给药周期的平均剂量强度为22.5mg/m²/周，这接近每月100mg/m²大剂量给药所达到的剂量强度。吉西他滨起始剂量为1000mg/m²（剂量水平1和2），然后每周递增250mg/m²，直至1750mg/m²（剂量水平5）。入组的32例初治化疗患者（22例男性，10例女性；中位年龄61岁，范围29 - 74岁）中，11例有局限性肿瘤（2例IIIA期，9例IIIB期），21例有IV期肿瘤伴血行转移且预后不良。21例为腺癌，4例为鳞状细胞癌，6例为大细胞未分化肿瘤，1例为鳞腺癌混合。在任何剂量水平的第1周期中，不止1例患者出现剂量限制性毒性。4级粒细胞减少和血小板减少在重复给药时更频繁发生，除最低剂量水平（顺铂25mg/m²，吉西他滨1000mg/m²）外，均需降低剂量。非血液学毒性较轻且可迅速逆转。与单独使用吉西他滨相比，顺铂给药导致恶心和呕吐的频率更高，但使用止吐药很容易控制。在可评估的28例患者中，到目前为止，大多数剂量水平都观察到了反应，总反应率为35.7%。这项I期试验正在进行中，进一步的剂量递增旨在确定吉西他滨的最大耐受剂量。
