Long Harry J, Rayson Sandra, Podratz Karl C, Abu-Ghazaleh Samir, Suman Vera, Hartmann Lynn C, Levitt Ralph, Nair Suresh, Hatfield Alan K, Knost James A
Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Am J Clin Oncol. 2002 Dec;25(6):547-51. doi: 10.1097/00000421-200212000-00002.
A randomized phase III study was conducted to assess the addition of molgramostim (GM-CSF) to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in terms of response rate, progression-free survival, and survival in women with advanced, recurrent, or metastatic carcinoma of the cervix or vagina. Patients received four 4-week cycles of methotrexate 30 mg/m2 IV days 1, 15, 22; vinblastine 3 mg/m2 IV days 2, 15, 22; doxorubicin 30 mg/m2 IV day 2; and cisplatin 70 mg/m2 IV day 2 with or without GM-CSF 5 microg/kg every 12 hours subcutaneously days 3 to 12. They were then reevaluated for operability. Those who were not surgical candidates were offered additional chemotherapy until progression or toxicity. Those who were surgical candidates were offered surgical resection of remaining tumor followed by involved-field external beam irradiation to sites of no prior irradiation and intraoperative irradiation to sites of prior external beam irradiation. This trial closed after 36 eligible patients were entered because of poor accrual. Although more than 40% of patients on each arm received fewer than four cycles of MVAC, the clinical response rate was 78% (95% CI: 52-94%) and 50% (95% CI: 26-74%) for MVAC and MVAC + GM-CSF, respectively; the median time to progression was 10.2 and 11.8 months, respectively; and median survival was 13.8 and 16.0 months, respectively. Toxicity was substantial, with more than 40% experiencing grade III to IV leukopenia, and nearly 40% experiencing grade III to IV stomatitis. MVAC with or without GM-CSF support achieves high response rates in patients with advanced, recurrent, or metastatic cervical carcinoma despite dose reductions and deletions. Its progression-free survival and overall survival rates appear promising. These results need to be confirmed within a large randomized phase III clinical trial.
开展了一项随机 III 期研究，以评估在甲氨蝶呤、长春碱、多柔比星和顺铂（MVAC）联合方案基础上加用莫拉司亭（GM-CSF）对晚期、复发或转移性子宫颈癌或阴道癌女性患者的缓解率、无进展生存期和总生存期的影响。患者接受四个 4 周周期的治疗，甲氨蝶呤 30 mg/m²，静脉注射，第 1、15、22 天；长春碱 3 mg/m²，静脉注射，第 2、15、22 天；多柔比星 30 mg/m²，静脉注射，第 2 天；顺铂 70 mg/m²，静脉注射，第 2 天，第 3 至 12 天每 12 小时皮下注射 GM-CSF 5 μg/kg，有或无 GM-CSF。然后对患者的可手术性进行重新评估。那些不适合手术的患者接受额外化疗，直至疾病进展或出现毒性反应。那些适合手术的患者接受剩余肿瘤的手术切除，随后对未接受过放疗的部位进行累及野体外照射，对接受过体外照射的部位进行术中照射。由于入组情况不佳，在纳入 36 例符合条件的患者后该试验结束。尽管每组中超过 40%的患者接受的 MVAC 周期少于四个，但 MVAC 和 MVAC + GM-CSF 的临床缓解率分别为 78%（95%CI：52 - 94%）和 50%（95%CI：26 - 74%）；中位无进展生存期分别为 10.2 个月和 11.8 个月；中位总生存期分别为 13.8 个月和 16.0 个月。毒性反应严重，超过 40%的患者出现 III 至 IV 级白细胞减少，近 40%的患者出现 III 至 IV 级口腔炎。无论有无 GM-CSF 支持，MVAC 方案在晚期、复发或转移性子宫颈癌患者中均可实现较高的缓解率，尽管存在剂量减少和删减情况。其无进展生存期和总生存率似乎很有前景。这些结果需要在大型随机 III 期临床试验中得到证实。
