Berek J S, Welander C, Schink J C, Grossberg H, Montz F J, Zigelboim J
Department of Obstetrics and Gynecology, UCLA School of Medicine 90024.
Gynecol Oncol. 1991 Mar;40(3):237-43. doi: 10.1016/0090-8258(90)90284-r.
A toxicity, dose, and schedule study of intraperitoneal (ip) cisplatin and alpha-interferon was conducted as a salvage therapy for patients with persistent, advanced epithelial ovarian cancer after primary systemic therapy with cisplatin-combination chemotherapy. Twenty-four patients were entered into this prospective, nonrandomized phase I-II trial conducted at two institutions following a uniform protocol. Cisplatin doses were escalated from 45 to 90 mg/m2, and alpha-interferon doses were escalated from 10 to 50 x 10(6) IU. At protocol entry, 4 (16%) patients had microscopic residual disease at second-look laparotomy, 5 (21%) had minimal residual disease less than 5 mm, 7 (30%) had residual disease 5-20 mm, and 8 (33%) had bulky residual disease greater than 20 mm. Toxicity was acceptable overall. Hematopoietic toxicity included a grade 3 total white cell count in 12% of courses when the cisplatin dose was equal to or greater than 60 mg/m2. Renal toxicity was modest with grade 2 toxicity in 20% of courses with a cisplatin dose greater than 60 mg/m2. Gastrointestinal toxicity, especially nausea and vomiting was seen in most courses; however, it was grade 3 and dose-limiting in greater than 30% of courses with cisplatin 75-90 mg/m2. General malaise, fever, flu-like symptoms, chills, and myalgias were seen in most courses, but it was dose-limiting (grade 3) toxicity in 6-11% of cycles when the dose of interferon was 25-50 x 10(6) IU. There was no grade 4 toxicity. Thus, the maximum tolerated dose (MTD) of the combination is 60 mg/m2 cisplatin and 25 x 10(6) IU interferon. Eighteen patients were evaluable for response, 15 of whom had responded to prior cisplatin therapy and 3 had not. Of the 10 patients evaluable for clinical response, one patient (10%) achieved a complete response (CCR), and one (10%) had a partial response (PCR). The progression free interval (PFI) and survival were 11 months and 19 months, respectively, for the CCR patient, 6 and 11 months, respectively, for the PCR patient, and the mean survival for nonresponders was 8 months. The other 8 patients underwent a reassessment laparotomy: 2 (25%) achieved a complete pathologic response (CPR), and 3 (38%) had a partial pathologic response (PPR). Both pathologic responses were in patients with minimal residual disease less than 5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)
进行了一项关于腹腔内（ip）顺铂和α-干扰素的毒性、剂量及给药方案的研究，将其作为顺铂联合化疗的一线全身治疗后持续性晚期上皮性卵巢癌患者的挽救疗法。24例患者按照统一方案进入在两家机构进行的这项前瞻性、非随机的I-II期试验。顺铂剂量从45mg/m²逐步递增至90mg/m²，α-干扰素剂量从10×10⁶IU逐步递增至50×10⁶IU。在方案入组时，4例（16%）患者在二次剖腹探查时有微小残留病灶，5例（21%）有小于5mm的微小残留病灶，7例（30%）有5 - 20mm的残留病灶，8例（33%）有大于20mm的大块残留病灶。总体毒性是可接受的。造血毒性方面，当顺铂剂量等于或大于60mg/m²时，12%的疗程出现3级全白细胞计数。肾毒性较轻，顺铂剂量大于60mg/m²时，20%的疗程出现2级毒性。大多数疗程出现胃肠道毒性，尤其是恶心和呕吐；然而，顺铂剂量为75 - 90mg/m²时，超过30%的疗程出现3级且剂量限制性毒性。大多数疗程出现全身不适、发热、流感样症状、寒战和肌痛，但当干扰素剂量为25 - 50×10⁶IU时，6 - 11%的周期出现剂量限制性（3级）毒性。无4级毒性。因此，联合用药的最大耐受剂量（MTD）是顺铂60mg/m²和干扰素25×10⁶IU。18例患者可评估疗效，其中15例曾对先前的顺铂治疗有反应，3例无反应。在可评估临床疗效的10例患者中，1例患者（10%）达到完全缓解（CCR），1例（10%）有部分缓解（PCR）。CCR患者的无进展生存期（PFI）和生存期分别为11个月和19个月，PCR患者分别为6个月和11个月，无反应者的平均生存期为8个月。另外8例患者接受了再次剖腹探查：2例（25%）达到完全病理缓解（CPR），3例（38%）有部分病理缓解（PPR）。两种病理缓解均出现在微小残留病灶小于5mm的患者中。（摘要截断于400字）
