Shin E, Ishitobi M, Hiraoia M, Kazumasa F, Hideyuki M, Nishisho I, Toshiro S, Yasunori H, Tosimasa T
Department of Surgery, Osaka National Hospital, Hoenzaka 2-1-14, Chyuo-ku, Osaka 540-0006, Japan.
Anticancer Res. 2000 Nov-Dec;20(6C):4721-6.
To find a more convenient and tolerable schedule than the tri-weekly or weekly schedules, we conducted a dose escalation study of bi-weekly docetaxel.
Between March 1998 and June 1999, 16 patients entered this phase I study. The starting dose was 40 mg/m2, with planned dose escalation to 45, 50 and 55 mg/m2, in consecutive patient cohorts. Patients continued to receive the assigned treatment at the same dose level bi-weekly, provided that they did not develop progressive disease, refuse further treatment, or experience unacceptable toxicity.
Grade 4 neutropenia lasting for more 4 days was seen at dose level 3 in all three patients. Only one patient who had previously received intensive chemotherapy required granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever and there were no actual episodes of neutropenic fever. Grade 3 asthenia and Grade 3 elevation of serum glutamic oxaloacetic transaminase were noted in only one patient treated at a dose of 40 mg/m2. Grade 3 skin toxicity and grade 2 elevation of serum glutamic oxaloacetic transaminase were seen in only one patient treated at a dose of 55 mg/m. Cumulative toxicity was not severe in all patients. Although grade 3 and/or grade 4 neutropenia were noted in eight patients (50%), all except one who received treatment at dose of 55 mg/m2 did not need G-CSF. Nail toxicity and peripheral edema seemed to be related to the number of treatment cycles. Severe fatigue and asthenia were never seen in all patients.
为了找到一种比每三周或每周给药方案更方便且耐受性更好的给药方案，我们开展了一项多西他赛每两周给药的剂量递增研究。
1998年3月至1999年6月，16例患者进入该I期研究。起始剂量为40mg/m²，计划在连续的患者队列中将剂量递增至45、50和55mg/m²。患者只要未出现疾病进展、拒绝进一步治疗或出现不可接受的毒性反应，就继续每两周接受相同剂量水平的指定治疗。
在剂量水平3时，所有3例患者均出现持续超过4天的4级中性粒细胞减少。只有1例先前接受过强化化疗的患者需要粒细胞集落刺激因子（G-CSF）来预防中性粒细胞减少性发热，且未实际发生中性粒细胞减少性发热。仅1例接受40mg/m²剂量治疗的患者出现3级乏力和3级血清谷草转氨酶升高。仅1例接受55mg/m²剂量治疗的患者出现3级皮肤毒性和2级血清谷草转氨酶升高。所有患者的累积毒性均不严重。虽然8例患者（50%）出现3级和/或4级中性粒细胞减少，但除1例接受55mg/m²剂量治疗的患者外，其余患者均不需要G-CSF。指甲毒性和外周水肿似乎与治疗周期数有关。所有患者均未出现严重疲劳和乏力。
1）按每两周给药方案给药时，多西他赛的最大耐受剂量为55mg/m²；2）多西他赛每两周给药耐受性良好。
