Bhatia Ashima, Tripathi K D, Sharma Manoj
Department of Pharmacology, Maulana Azad Medical College, New Delhi, India.
Indian J Med Res. 2003 Jul;118:33-41.
BACKGROUND & OBJECTIVES: Nausea and vomiting remain the most distressing side effects of cancer chemotherapy. The present study aimed to study the efficacy and tolerability of ondansetron versus (vs) metoclopramide in different dose related grades of cisplatin induced acute emesis.
A total of 137 patients were enrolled and 80 completed the study. Cisplatin 60 mg/m2 was given intravenously (iv) either as a single dose on day 1 (high dose regimen) or in three doses of 20 mg/m2 each on days 1-3 (low dose regimen) along with bleomycin +5-flurouracil in 40 patients each. Patients were randomized in each cisplatin regimen to receive either 20 mg metoclopramide (20 patients) or 8 mg ondansetron (20 patients) iv 30 min prior to cisplatin administration followed by 20 mg metoclopramide or 8 mg ondansetron orally 8 h respectively for 24 h after the last cisplatin administration. Ten patients receiving high dose cisplatin in each group were also given dexamethasone 8 mg iv with the primary antiemetic. Patients were assessed for 24 h after the last cisplatin injection.
In low dose cisplatin regimen, complete suppression of acute emesis occurred in 65 per cent patients receiving ondansetron versus 30 per cent receiving metoclopramide, while in high dose regimen, complete response rate was 20 per cent with ondansetron versus 0 per cent with metoclopramide. Dexamethasone significantly augmented the antiemetic efficacy of metoclopramide but not that of ondansetron. Protection from nausea in the acute phase was seen in 95 per cent patients receiving ondansetron vs 70 per cent receiving metoclopramide in low dose regimen. With high dose the protection rates were 90 vs 0 per cent respectively. Combination of dexamethasone + metoclopramide achieved 70 per cent protection while dexamethasone + ondansetron was effective in 90 per cent. Dropouts and withdrawals were more among patients receiving high dose cisplatin and antiemetic regimens without dexamethasone. Thirty nine adverse events were reported by 20 out of 80 patients. All adverse events were mild.
INTERPRETATION & CONCLUSION: The results demonstrate dose related emetogenicity of cisplatin and superior antiemetic efficacy of ondansetron, especially against high dose cisplatin regimen. Dexamethasone potentiated efficacy of metoclopramide but not that of ondansetron. The combination of metoclopramide plus dexamethasone was found to be as efficacious as ondansetron monotherapy.
恶心和呕吐仍是癌症化疗最令人苦恼的副作用。本研究旨在探讨昂丹司琼与甲氧氯普胺在不同剂量相关等级的顺铂所致急性呕吐中的疗效和耐受性。
共纳入137例患者，80例完成研究。40例患者接受顺铂60mg/m²静脉注射，第1天单次给药（高剂量方案）或第1 - 3天每天3次每次20mg/m²给药（低剂量方案），同时联合博来霉素和5 - 氟尿嘧啶。每种顺铂方案的患者随机分为两组，分别在顺铂给药前30分钟静脉注射20mg甲氧氯普胺（20例患者）或8mg昂丹司琼（20例患者），最后一次顺铂给药后8小时分别口服20mg甲氧氯普胺或8mg昂丹司琼，持续24小时。每组接受高剂量顺铂的10例患者还在使用主要止吐药时静脉注射8mg地塞米松。在最后一次顺铂注射后对患者进行24小时评估。
在低剂量顺铂方案中，接受昂丹司琼的患者急性呕吐完全抑制率为65%，而接受甲氧氯普胺的为30%；在高剂量方案中，昂丹司琼的完全缓解率为20%，甲氧氯普胺为0%。地塞米松显著增强了甲氧氯普胺的止吐效果，但未增强昂丹司琼的效果。低剂量方案中，95%接受昂丹司琼的患者在急性期免受恶心困扰，接受甲氧氯普胺的为70%。高剂量时，保护率分别为90%和0%。地塞米松 + 甲氧氯普胺联合方案的保护率为70%，地塞米松 + 昂丹司琼为90%。接受高剂量顺铂且未使用地塞米松的止吐方案的患者中，退出和失访的更多。80例患者中有20例报告了39例不良事件。所有不良事件均为轻度。
结果表明顺铂的致吐性与剂量相关，昂丹司琼的止吐效果更佳，尤其是针对高剂量顺铂方案。地塞米松增强了甲氧氯普胺的疗效，但未增强昂丹司琼的疗效。发现甲氧氯普胺加地塞米松的联合方案与昂丹司琼单药治疗效果相当。
