Frasci G, Panza N, Comella P, Cartení G, Guida T, Nicolella G P, Natale M, Lombardi R, Apicella A, Pacilio C, Gravina A, Lapenta L, Comella G
Department of Diagnostic Imaging, National Tumor Institute, Naples, Italy.
Ann Oncol. 1999 Mar;10(3):355-8. doi: 10.1023/a:1008301222560.
Paclitaxel (PTX) and topotecan (TPT) have shown promising antitumor activity in both ovarian cancer (OC) and small-cell lung cancer (SCLC) patients. This phase I study was aimed at determining the maximum tolerable dose (MTD) of TPT given weekly over 30 min in combination with fixed doses of cisplatin (CDDP) and (PTX), and with G-CSF support.
Forty-four patients with OC (19) or SCLC (25), either chemo-naïve (20) or pretreated (24) received CDDP 40 mg/m2, PTX 85 mg/m2 (one-hour infusion) and escalating TPT doses (starting from 0.75 mg/m2) in a 30-min infusion in weekly administration. Filgrastim 5 mg/kg was administered on days 3 to 5 of each week.
Eight different dose levels were tested for a total of 295 delivered cycles. The dose escalation was interrupted at the TPT dose of 2.50 mg/m2. No toxic deaths occurred in this study. Grade 3 to 4 neutropenia, thrombocytopenia, and anemia occurred in 15 patients (36 cycles), seven patients (15 cycles), and four patients (five cycles), respectively. Severe vomiting and diarrhoea occurred in seven and four patients. Peripheral neuropathy was recorded in 11 patients (42 cycles), but it was never severe. An overall 11 of 19 (58%) OC and 11 of 25 (44%) SCLC patients obtained objective responses. Eight patients showed complete responses (three OC and three SCLC). Among the 20 chemo-naïve patients, 9 of 11 (82%) OC and seven of nine (78%) SCLC responded.
The CDDP/TPT/PTX weekly administration with filgrastim support represents a well-tolerated and active therapeutic approach in both chemo-naïve and pretreated OC and SCLC patients. A weekly dose of TPT of 2.25 mg/m2 is recommended for the phase II study.
紫杉醇（PTX）和拓扑替康（TPT）在卵巢癌（OC）和小细胞肺癌（SCLC）患者中均显示出有前景的抗肿瘤活性。本I期研究旨在确定每周30分钟静脉输注TPT联合固定剂量顺铂（CDDP）和（PTX）并给予粒细胞集落刺激因子（G-CSF）支持时的最大耐受剂量（MTD）。
44例OC患者（19例）或SCLC患者（25例），其中初治患者（20例）或经治患者（24例），接受CDDP 40mg/m²、PTX 85mg/m²（1小时输注）以及递增剂量的TPT（从0.75mg/m²开始），每周静脉输注30分钟。每周第3至5天给予非格司亭5mg/kg。
共测试了8个不同剂量水平，总计295个给药周期。在TPT剂量为2.50mg/m²时中断剂量递增。本研究中未发生毒性死亡。15例患者（36个周期）出现3至4级中性粒细胞减少，7例患者（15个周期）出现血小板减少，4例患者（5个周期）出现贫血。7例和4例患者分别出现严重呕吐和腹泻。11例患者（42个周期）记录到周围神经病变，但均不严重。19例OC患者中有11例（58%）、25例SCLC患者中有11例（44%）获得客观缓解。8例患者出现完全缓解（3例OC和3例SCLC）。在20例初治患者中，11例OC患者中有9例（82%）、9例SCLC患者中有7例（78%）有反应。
在初治和经治的OC和SCLC患者中，每周给予CDDP/TPT/PTX并给予非格司亭支持是一种耐受性良好且有效的治疗方法。II期研究推荐TPT每周剂量为2.25mg/m²。
