Stehman F B, Bundy B N, Kucera P R, Deppe G, Reddy S, O'Connor D M
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, USA.
Gynecol Oncol. 1997 Aug;66(2):262-7. doi: 10.1006/gyno.1997.4761.
In a previous study, the Gynecologic Oncology Group (GOG) compared hydroxyurea (HDXR) and the combination of cisplatin (C) and 5-fluorouracil (5-FU) infusion as potentiators of radiation therapy. This study was undertaken to determine whether these two regimens could be combined, concurrent with pelvic radiation therapy in patients with locally advanced cervical cancer.
The GOG entered 75 eligible and evaluable patients on a Phase I-II evaluation of HDXR, C, and 5-FU as adjuncts to radiation therapy for locally advanced carcinoma of the cervix. All patients had histologically verified primary disease and confirmed negative para-aortic lymph nodes. Eligibility was limited to clinical stage IIB through IVA. HDXR was given orally, twice weekly at a dose of 2.5 g/m2; C on Days 1 and 29 at 50 mg/m2; and 5-FU by 96-hr infusion on Days 2-5 and 30-33 at a starting dose of 800 mg/m2.
Forty-eight (64%) patients had stage IIB disease, 25 (33%) had stage IIIB, and 2 had stage IVA tumors. Primary tumors 4 cm or less in size were present in 15 patients, between 4 and 6 cm were in 27 patients, and larger than 6-cm were observed in 33 patients. Grade 3/4 acute toxicity was experienced by 41 (54.7%) patients. These acute toxicities caused delays in prescribed radiation therapy of more than 1 week in 14 (18.9%) and low doses of drug in 16 (21.3%), and only 26 (34.7%) patients had the scheduled dose escalation of 5-FU on their second course. Clinical response was excellent with complete and partial response rate of 93.3%. Median time to progression has not been reached.
Although this dose and schedule could be successfully administered, the delays in therapy should be avoided by a lower starting dose of hydroxyurea. Stomatitis was not a dose-limiting toxicity. These results have formed the basis of a phase III trial comparing this regimen to two other chemoradiation regimens.
在之前的一项研究中，妇科肿瘤学组（GOG）比较了羟基脲（HDXR）以及顺铂（C）与5-氟尿嘧啶（5-FU）联合输注作为放射治疗增效剂的效果。本研究旨在确定这两种方案能否与盆腔放射治疗同时联合应用于局部晚期宫颈癌患者。
GOG纳入了75例符合条件且可评估的患者，对HDXR、C和5-FU作为局部晚期宫颈癌放射治疗辅助手段进行I-II期评估。所有患者均经组织学证实为原发性疾病且腹主动脉旁淋巴结证实为阴性。入选标准限于临床分期IIB至IVA期。HDXR口服给药，每周两次，剂量为2.5 g/m²；C在第1天和第29天给药，剂量为50 mg/m²；5-FU在第2 - 5天和第30 - 33天进行96小时输注，起始剂量为800 mg/m²。
48例（64%）患者为IIB期疾病，25例（33%）为IIIB期，2例为IVA期肿瘤。15例患者原发性肿瘤大小为4 cm或更小，27例患者肿瘤大小在4至6 cm之间，33例患者肿瘤大于6 cm。41例（54.7%）患者出现3/4级急性毒性反应。这些急性毒性反应导致14例（18.9%）患者规定的放射治疗延迟超过1周，16例（21.3%）患者药物剂量降低，只有26例（34.7%）患者在第二个疗程中按计划增加了5-FU剂量。临床反应良好，完全缓解和部分缓解率为93.3%。中位进展时间尚未达到。
尽管该剂量和方案能够成功实施，但通过降低羟基脲的起始剂量应避免治疗延迟。口腔炎并非剂量限制性毒性反应。这些结果构成了一项III期试验的基础，该试验将此方案与其他两种放化疗方案进行比较。
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