Baranzelli M C, Pichon F, Gourmel B, N'Guyen M, Deligny N, Demaille M C
Service d'oncologie médicale A, Centre Oscar-Lambrel, France.
Bull Cancer. 1997 Feb;84(2):141-6.
Ifosfamide is one of the most efficient antimitotic in soft tissue sarcoma. To try to find a possible dose-effect, 10 patients with advanced pretraited relapsed soft tissue sarcoma received 15 g/m2/cycle ifosfamide in continuous infusion during 5 days. A pharmacokinetic study was done for 2 patients. All patients received growth factors, ondansetron and 8 clonazepam. Renal toxicity was evaluated after the first and the second cycle. Twenty two cycles were delivered to patients who have been already treated with ifosfamid (10 patients with 15 g/m2 to 54 g/m2, median 27 g/m2) or cis platinum (2 patients). No major renal or neurologic toxicity was observed; only subclinical modifications of urinary enzymes excretion were found. Two patients had visual hallucinations at the end of a cycle and just in the 2 following days; another presented a neuropathy of inferior limbs. Hematological toxicity was very limited. Pharmacokinetic study did not show induction mechanism at this dosage and with this type of administration. So ifosfamide 3 g/m2 during 5 days is feasible. The few level of complications observed is perhaps linked to the daily dose of 3 g/m2 instead of 4 g/m2 or more used in the other studies.
异环磷酰胺是软组织肉瘤中最有效的抗有丝分裂药物之一。为了探寻可能的剂量效应，10例晚期经预处理后复发的软组织肉瘤患者接受了15g/m²/周期的异环磷酰胺持续静脉输注，共5天。对2例患者进行了药代动力学研究。所有患者均接受了生长因子、昂丹司琼和8片氯硝西泮治疗。在第一个和第二个周期后评估肾毒性。共对已接受异环磷酰胺（10例，剂量为15g/m²至54g/m²，中位数为27g/m²）或顺铂（2例）治疗的患者进行了22个周期的治疗。未观察到严重的肾毒性或神经毒性；仅发现尿酶排泄有亚临床改变。2例患者在一个周期结束时及随后两天出现视幻觉；另1例出现下肢神经病变。血液学毒性非常有限。药代动力学研究未显示在此剂量及这种给药方式下存在诱导机制。因此，5天内给予3g/m²的异环磷酰胺是可行的。观察到的并发症较少，这可能与每日3g/m²的剂量有关，而其他研究中使用的剂量为4g/m²或更高。
