Mehta Vivek K, Cho Cheryl, Ford James M, Jambalos C, Poen Joseph, Koong Albert, Lin Albert, Bastidas J Augusto, Young Harvey, Dunphy Eamonn P, Fisher George
Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):132-7. doi: 10.1016/s0360-3016(02)03863-4.
CPT-11 sensitizes tumor cells to radiation and in combination therapy with 5-fluorouracil (5-FU) results in enhanced cytotoxicity to metastatic colorectal cancer. We report the results from a Phase II trial of preoperative radiotherapy (RT), CPT-11, and 5-FU for patients with ultrasound-staged T3 rectal cancer.
Between April 1999 and August 2001, 32 patients (21 men, 11 women; median age 52 years, range 40-74) with biopsy-proven adenocarcinoma of the rectum were enrolled in the study. All patients underwent endorectal ultrasonography for staging (uT3N0 = 19; uT3N1 = 13; uT2N1 = 1). RT was prescribed to the draining lymph nodes (45 Gy in 1.8-Gy daily fractions) and tumor (50.4 Gy in 1.8-Gy daily fractions). Patients also received concurrent CPT-11 (50 mg/m(2), Days 1, 8, 15, and 22) and 5-FU (200 mg/m(2) daily, 7 d/wk, Days 1-33). Surgical resection was performed 6-10 weeks after completing chemoradiotherapy.
Acute toxicity was frequently observed, and 18 patients (56%) required either a chemotherapy dose reduction or RT interruption of >3 days. One patient withdrew because of diarrhea and abdominal cramping (Grade III) after 10 days of treatment. Although no Grade IV toxicity was observed, Grade III diarrhea (n = 9, 28%), mucositis (n = 7, 21%), rectal sores (n = 7, 21%), abdominal cramping (n = 3, 9%) were noted. Of the 32 patients who underwent surgery, 12 had a complete pathologic response. Of the 32 patients, the disease of 23 (71%) was downstaged. The average length of hospitalization was between 5 and 12 days, with 1 patient staying 33 days. All patients were followed for disease-free survival.
Although associated with frequent acute toxicity, the regimen is associated with significant tumor "downstaging." Additional patients and longer follow-up are necessary to define the role of this regimen fully.
CPT - 11可使肿瘤细胞对放疗敏感，与5 - 氟尿嘧啶（5 - FU）联合治疗可增强对转移性结直肠癌的细胞毒性。我们报告了一项针对超声分期为T3期直肠癌患者的术前放疗（RT）、CPT - 11和5 - FU的II期试验结果。
1999年4月至2001年8月，32例经活检证实为直肠腺癌的患者（21例男性，11例女性；中位年龄52岁，范围40 - 74岁）纳入本研究。所有患者均接受直肠内超声检查以进行分期（超声T3N0 = 19例；超声T3N1 = 13例；超声T2N1 = 1例）。放疗处方剂量为引流淋巴结（45 Gy，每日1.8 Gy分次）和肿瘤（50.4 Gy，每日1.8 Gy分次）。患者还同时接受CPT - 11（50 mg/m²，第1、8、15和22天）和5 - FU（每日200 mg/m²，每周7天，第1 - 33天）。在完成放化疗后6 - 10周进行手术切除。
经常观察到急性毒性反应，18例患者（56%）需要降低化疗剂量或中断放疗超过3天。1例患者在治疗10天后因腹泻和腹部绞痛（III级）退出研究。尽管未观察到IV级毒性反应，但观察到III级腹泻（n = 9，28%）、黏膜炎（n = 7，21%）、直肠溃疡（n = 7，21%）、腹部绞痛（n = 3，9%）。在接受手术的32例患者中，12例有完全病理缓解。在32例患者中，23例（71%）疾病分期降低。平均住院时间为5至12天，1例患者住院33天。所有患者均进行无病生存期随访。
尽管该方案常伴有急性毒性反应，但与显著的肿瘤“降期”相关。需要更多患者和更长时间的随访来全面确定该方案的作用。
