De Placido S, Tramontana S, Ferrari E, De Matteis A, Lauria R, Perrone F, Bianco A R, Gallo C, Ricchi P, De Placido G, Pignata S
Cattedra di Oncologia Medica, Università Federico II, via S. Pansini 5, 80131, Napoli, Italy.
Anticancer Res. 2000 Sep-Oct;20(5C):4023-9.
Prognosis of advanced ovarian cancer is unsatisfactory. Chemotherapy can be intensified combining active drugs at their highest possible doses.
In this phase I/II trial, 77 untreated patients received escalating doses of paclitaxel (135, 155, 175, 195 and 215 mg/m2, infused over 3 hours) with carboplatin (AUC 3.6) and cisplatin (60 mg/m2). Nine, 16, 13, 8 and 3 patients were treated at the five levels, respectively. A further 28 patients were treated at the maximum tolerable dose (MTD).
Dose-limiting toxicities (one WHO grade 3 constipation, one grade 2 prolonged peripheral neurotoxicity and one grade 3 cardiac toxicity) occurred at 215 mg/m2 in 3 out of 3 patients. MTD was reached at level 4 paclitaxel dose (195 mg/m2). Response was evaluated in 62 patients. A complete response was achieved in 23 patients (37.1%-95% CI 25.2-50.3), including 16 (25.8%) pathological and partial response in 28 (45.2%), for an overall response rate of 82.3% (95% exact CL: 70.5%-90.8%). The probability of response was affected by the degree of initial debulking (p = 0.002) and not by the paclitaxel dose. In patients with stage III-IV disease, median progression-free survival was 17 months (95% CI 14-25). After a median follow-up of 28 months, median survival had not been reached; 2-year estimated survival was 67%.
Paclitaxel can be safely given at the dose of 195 mg/m2 in combination with carboplatin (AUC 3.6) and cisplatin (60 mg/m2). This combination is active and safe and could be considered in clinical settings requiring intensive short treatment.
晚期卵巢癌的预后不尽人意。可通过联合使用尽可能高剂量的活性药物来强化化疗。
在这项I/II期试验中，77例未经治疗的患者接受了递增剂量的紫杉醇（135、155、175、195和215mg/m²，静脉滴注3小时）联合卡铂（AUC 3.6）和顺铂（60mg/m²）治疗。五个剂量水平分别治疗了9例、16例、13例、8例和3例患者。另外28例患者接受了最大耐受剂量（MTD）治疗。
在215mg/m²剂量水平，3例患者中有3例出现剂量限制性毒性（1例世界卫生组织3级便秘、1例2级外周神经毒性延长和1例3级心脏毒性）。在紫杉醇剂量水平4（195mg/m²）时达到了MTD。对62例患者进行了疗效评估。23例患者获得完全缓解（37.1%，95%CI 25.2 - 50.3），其中16例（25.8%）为病理完全缓解，28例（45.2%）为部分缓解，总缓解率为82.3%（95%精确CL：70.5% - 90.8%）。缓解概率受初始肿瘤减灭程度的影响（p = 0.002），而不受紫杉醇剂量的影响。在III - IV期疾病患者中，无进展生存期的中位数为17个月（95%CI 14 - 25）。经过28个月的中位随访，总生存期的中位数尚未达到；2年估计生存率为67%。
紫杉醇可安全地以195mg/m²的剂量与卡铂（AUC 3.6）和顺铂（60mg/m²）联合使用。这种联合方案有效且安全，在需要强化短期治疗的临床环境中可予以考虑。
