Paccagnella A, Favaretto A, Oniga F, Festi G, Lauro S, Morabito A, Ossana L, Sartore F, DePoli F, Fiorentino M V
Divislone di Oncologia Medica, Azienda Ospedaliera di Padova, Italy.
Cancer. 1996 Oct 15;78(8):1701-7.
The mitomycin C, vinblastine, and cisplatin (MVP) combination is one of the most frequently used in the palliative setting, but it produces considerable toxicity. Carboplatin and cisplatin have different patterns of toxicity. The goal of this study was to evaluate a combination similar to MVP, using carboplatin instead of cisplatin to render it more feasible in an outpatient setting.
Inclusion criteria for this study included: inoperable patients or patients relapsing after previous surgery, with nonsmall cell lung carcinoma (NSCLC), a performance status (PS) > 50%, and no previous chemotherapy. The chemotherapy regimen included carboplatin, 300 mg/m2 on Day 1; mitomycin, 8 mg/m2 on Day 1; and vinblastine, 4 mg/m2 on Days 1, 8, and 15 (on Day 15 vinblastine was delivered only in the first cycle) (MVC) every 3 weeks for at least 3 cycles.
From August 1991 until August 1994, 70 patients entered the trial. All were evaluable for toxicity and response. The median age was 62 years (range, 40-73 years). The male/female ratio was 60:10 (86%:14%); the ratio of Stage III to Stage IV disease was 26:44 (37%:63%); and the ratio of PS > 70 to < or = 70 was 49:21. A total of 296 cycles (median, 4 [range, 1-6 cycles] per patient) were delivered, 280 of 296 (95%) in an outpatient setting with only 4 patients requiring hospitalization for treatment delivery. Overall response rate (RR) was 38.6% (95% confidence interval [CI], 27-51%) (1 complete response, 1.5%; 26 partial responses, 37.1%). Median duration of response was 9.8 months (range, 2-27 months). In Stage III patients the RR was 42% and in Stage IV patients it was 34%. Overall median survival was 9.5 months (95% CI, 6.8-15.3 months). Survival at 1 year was 39% (standard error [SE] 3.6%) and was 11% at 2 years (SE 3.6%). In Stage III patients median survival was 13 months and the 1-year survival rate was 54% (SE 10%); Stage IV patients had a median survival of 7.4 months and a 1-year survival rate of 28% (SE 7%). Delivered dose intensity was: carboplatin, 71%; vinblastine, 60%; and mitomycin C, 77% of the planned dose intensity. The back calculation of carboplatin area under the curve (AUC) with Calvert's formula and with the Cockcroft-Gault glomerular filtration rate estimation, showed a median AUC value of 4 (range, 2-8). Using the more precise Chatelut formula, AUC was again 4 (range, 2-7). Hematologic toxicity was the major side effect; Grades 3 and 4 leukopenia were observed in 34% and 6% of patients, respectively, and Grades 3 and 4 thrombocytopenia in 25% and 4% of patients, respectively. Grade 2 infection occurred in 10% of patients, with only 1 case of sepsis; severe constipation and Grade 2 alopecia occurred in only 1 patient; and no case of higher than Grade 1 nephrotoxicity was observed. No pulmonary toxicity was observed. Compliance with treatment was good with only one patient refusal after the first cycle.
Chemotherapy for advanced NSCLS is still controversial, because effectiveness in terms of RR and symptom control must be weighed against treatment toxicity and costs. From our study it appears that MVC is easy to deliver in an outpatient setting, and has good patient compliance, low toxicity profile, and promising RR and response duration. The substitution of carboplatin for cisplatin in regimens for advanced NSCLC should be considered.
丝裂霉素C、长春碱和顺铂（MVP）联合方案是姑息治疗中最常用的方案之一，但会产生相当大的毒性。卡铂和顺铂的毒性模式不同。本研究的目的是评估一种类似于MVP的联合方案，用卡铂替代顺铂，使其在门诊环境中更可行。
本研究的纳入标准包括：无法手术的患者或既往手术后复发的患者，患有非小细胞肺癌（NSCLC），体能状态（PS）>50%，且既往未接受过化疗。化疗方案包括：第1天给予卡铂300mg/m²；第1天给予丝裂霉素8mg/m²；第1、8和15天给予长春碱4mg/m²（第15天长春碱仅在第1周期给药）（MVC），每3周进行1次，至少进行3个周期。
从1991年8月至1994年8月，70例患者进入试验。所有患者均可评估毒性和疗效。中位年龄为62岁（范围40 - 73岁）。男女比例为60:10（86%:14%）；Ⅲ期与Ⅳ期疾病的比例为26:44（37%:63%）；PS>70与≤70的比例为49:21。共进行了296个周期（中位，每位患者4个周期[范围1 - 6个周期]），296个周期中的280个（95%）在门诊进行，仅4例患者需要住院治疗。总缓解率（RR）为38.6%（95%置信区间[CI]，27 - 51%）（1例完全缓解，1.5%；26例部分缓解，37.1%）。中位缓解持续时间为9.8个月（范围2 - 27个月）。Ⅲ期患者的RR为42%，Ⅳ期患者为34%。总中位生存期为9.5个月（95%CI，6.8 - 15.3个月）。1年生存率为39%（标准误[SE] 3.6%），2年生存率为11%（SE 3.6%）。Ⅲ期患者的中位生存期为13个月，1年生存率为54%（SE 10%）；Ⅳ期患者的中位生存期为7.4个月，1年生存率为28%（SE 7%）。实际给药剂量强度为：卡铂71%；长春碱60%；丝裂霉素C为计划剂量强度的77%。用卡尔弗特公式和考克饶夫-高尔特肾小球滤过率估计法对卡铂曲线下面积（AUC）进行反向计算，显示中位AUC值为4（范围2 - 8）。使用更精确的沙泰勒公式，AUC再次为4（范围2 - 7）。血液学毒性是主要副作用；分别有34%和6%的患者观察到3级和4级白细胞减少，25%和4%的患者分别观察到3级和4级血小板减少。10%的患者发生2级感染，仅1例败血症；仅1例患者出现严重便秘和2级脱发；未观察到高于1级的肾毒性病例。未观察到肺部毒性。治疗依从性良好，仅1例患者在第1周期后拒绝治疗。
晚期NSCLS的化疗仍存在争议，因为在RR和症状控制方面的有效性必须与治疗毒性和成本相权衡。从我们的研究来看，MVC在门诊环境中易于给药，患者依从性好，毒性低，RR和缓解持续时间有前景。对于晚期NSCLC的治疗方案，应考虑用卡铂替代顺铂。
