MA13.11 A Randomized Phase III Study of Cisplatin-Polymeric Micelle Paclitaxel vs Cisplatin-Solvent-Based Paclitaxel in 1st Line Advanced NSCLC
Yi‐Long WuBaohui HanMeiqi ShiHai‐Yan TuAiqin GuCheng HuangHuili WangZhuang YuX. WangL. CaoYongqian ShuHui WangRunxiang YangXiaogang LiJinjia ChangYu HuPeng ShenYuan HuZhongliang GuoMin TaoYumin ZhangX. LiuQian SunX. ZhangZedong JiangJiuda ZhaoFeng ChenJing SunDi LiJian Zhou
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Abstract The established antitumor efficacy of paclitaxel and cisplatin as single agents and their distinctly different mechanisms of action have prompted laboratory and clinical research into their use in combination. Our in vivo study was performed to investigate the importance of sequence of administration and inter‐agent interval. C3Hf/Kam mice bearing OCa‐1 tumors received paclitaxel and cisplatin. The antitumor efficacy of the combination, measured as re‐growth delay and expressed as the enhancement factor (EF), was determined for inter‐agent intervals of I, 9, 24, 48 and 72 hr. Morphometric analysis was used to determine the contribution of induced apoptosis. Our findings showed an additive effect when cisplatin preceded paclitaxel by 1 and 24 hr, producing EF of 1.1 and 1.0, respectively, and a greater than additive effect for 9 and 48 hr, producing EF of 1.3 and 1.8, respectively. This sequence, however, was associated with significant morbidity and mortality. When paclitaxel preceded cisplatin the effect was greater than additive with the EF for I, 9 and 24 hr, being 1.2, 1.5 and 1.5, respectively, and increasing to a maximum of 1.9 at 48 hr. Thus, for this combination, the therapeutic ratio was improved when paclitaxel preceded cisplatin and was greatest when a 48 hr interval was allowed between drugs. We were unable to attribute the efficacy of the drug combination to increased induction of apoptosis and suggest other possible mechanisms. © 1995 Wiley‐Liss, Inc.
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Refractory (planetary science)
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Nucleoside analogue
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Drug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated
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目的将在周期性的颈的癌症的治疗加 cisplatin 观察 paclitaxel 的功效和毒性。方法有周期性的颈的癌症的诊断的 23 个病人是合格的。三周刊的化疗政体由 paclitaxel 组成了为白天 1 上的 3 h 的 135 150 mg/m2 注入， cisplatin 白天 1 ～ 3 上的 25 mg/m2 注入。所有病人接受了至少二周期治疗。反应评估的结果是 47.8% 包括 CR 2 盒子(8.7%) ， PR 9 盒子(39.1%) 。主要毒性包括了嗜中性白血球减少症，呕吐的恶心，关节痛，肌痛和脱发。与 cisplatin 相结合的结论 Paclitaxel 是有为周期性的颈的癌症的可接受的不利反应的有效治疗。
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Paclitaxel and cisplatin are associated with dose‐limiting neurotoxicity that may result from their differing effects on microtubule stability in peripheral nerves. We hypothesized that such different actions of paclitaxel and cisplatin could be exploited to minimize their neurotoxicity by giving them in combination. Paclitaxel (9–18 micromol/kg/week or 7.7–15.4 mg/kg/week) and cisplatin (5–10 micromol/kg/week or 1.5–3 mg/kg/week) were given alone and in combination to female Wistar rats. Treatment was given once per week for a total of 7–10 weeks. Paclitaxel and cisplatin were given 24 h apart when they were given in combination. Changes in sensory nerve conduction velocity (SNCV) and dorsal root ganglia (DRG) morphology were measured. The nature of their interaction was analyzed using an isobologram. Their antitumor activity alone or in combination was also determined in C57B1/6 mice bearing colon 38 tumors. Reductions in SNCV occurred with paclitaxel alone (P = 0.009), cisplatin alone (P = 0.012), and cisplatin given 24 h before paclitaxel (P < 0.0001). In contrast, there was no significant change in SNCV with paclitaxel given 24 h before cisplatin (P = 0.11). An isobologram showed that the SNCV effects of the drug combinations were less than additive or antagonistic. Cisplatin‐induced morphometric changes in DRG neurons were less marked when cisplatin was given with paclitaxel (P = 0.004). Concentrations of platinum in dorsal root ganglia, sural nerves, and sciatic nerves were not altered by giving paclitaxel before cisplatin. Tumor growth delays (TGD) were greater after treatment with paclitaxel (23.4 mu mol/kg or 20 mg/kg) given 24 h before cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 7.5 days) than after paclitaxel (23.4 micromol/kg or 20 mg/kg) (TGD = 2.0 days) or cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 3.5 days) alone. Paclitaxel and cisplatin antagonized each other's neurotoxicity in Wistar rats. Combining cytotoxic agents with opposing effects on peripheral nerves has potential for minimizing neurotoxicity in patients.
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