Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012

被引:205
作者
Mohiuddin, M
Winter, K
Mitchell, E
Hanna, N
Yuen, A
Nichols, C
Shane, R
Hayostek, C
Willett, C
机构
[1] Geisinger Canc Inst, Wilkes Barre, PA 18711 USA
[2] Thomas Jefferson Univ, Radiat Therapy Oncol Grp, Philadelphia, PA 19107 USA
[3] Reading Hosp Med Ctr, Reading, PA USA
[4] Univ Maryland, Med Ctr, Dept Surg Oncol, Baltimore, MD 21201 USA
[5] Bay Med Reg Canc Ctr, Panama City, FL USA
[6] Ingalls Mem Hosp, Harvey, IL USA
[7] Santa Fe Canc Ctr, Santa Fe, NM USA
[8] Duke Univ, Med Ctr, Durham, NC USA
关键词
D O I
10.1200/JCO.2005.03.6095
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose To evaluate the rate of pathologic complete response and toxicity of neoadjuvant chemoradiation for advanced T3/74 distal rectal cancers in a randomized phase II study Patients and Methods Patients with clinical T3/T4 distal rectal cancers were randomly assigned in a phase 11 study to receive combined neoadjuvant chemoradiotherapy followed by surgical resection. Patients were randomly assigned to receive continuous venous infusion (CVI) fluorouracil (FU) 225 mg/m(2) per day, 7 days per week, plus pelvic hyperfractionated radiation 55.2 to 60 Gy at 1.2 Gy bid (arm 1) or CVI FU 225 mg/m(2) per day Monday to Friday, 120 hours per week plus irinotecan 50 mg/m(2) once weekly for 4 weeks plus pelvic radiation therapy 50.4 to 54 Gy at 1.8 Gy per day (arm 2). Surgery was performed 4 to 10 weeks after completion of necadjuvant therapy. The primary end point of this study was pathologic complete response (pCR). Secondary end points included acute and late normal tissue morbidity. Results A total of 106 patients were entered onto the study, with 103 assessable for response. The overall resectability rate was 93%. The median time to surgery was 7 weeks. Tumor downstaging was observed in 78% of patients in both arms. The pCR rate for all assessable patients was 26% in each arm. For patients who had surgery, the pCR rate was also the same (28%) in both arms. Acute and late toxicity was also similar. Grade 3 and 4 acute hematologic and nonhematologic toxicity occurred in 13% and 38% in arm 1 and 12% and 45% in arm 2, respectively. Conclusion Although the overall complete response rate and toxicity seems similar in both arms, this is the first multi-institutional study to establish a relatively high (28%) pCR rate after neoadjuvant therapy.
引用
收藏
页码:650 / 655
页数:6
相关论文
共 37 条
[1]  
Bosset JF, 2004, J CLIN ONCOL, V22, p246S
[2]   Preoperative radiochemotherapy in rectal cancer: Long-term results of a phase II trial [J].
Bosset, JF ;
Magnin, V ;
Maingon, P ;
Mantion, G ;
Pelissier, EP ;
Mercier, M ;
Chaillard, G ;
Horiot, JC .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2000, 46 (02) :323-327
[3]   Response to preoperative chemoradiation in Stage II and III rectal cancer [J].
Brown, CL ;
Ternent, CA ;
Thorson, AG ;
Christensen, MA ;
Blatchford, GJ ;
Shashidharan, M ;
Haynatzki, GR .
DISEASES OF THE COLON & RECTUM, 2003, 46 (09) :1189-1193
[4]  
BYFIELD JE, 1997, P AM ASSOC CANC RES, V18, P74
[5]   PREOPERATIVE CONCURRENT 5-FLUOROURACIL INFUSION, MITOMYCIN-C AND PELVIC RADIATION-THERAPY IN TETHERED AND FIXED RECTAL-CARCINOMA [J].
CHAN, A ;
WONG, A ;
LANGEVIN, J ;
KHOO, R .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1993, 25 (05) :791-799
[6]   Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: A phase II dose escalation study [J].
Chan, AKP ;
Wong, AO ;
Langevin, J ;
Jenken, D ;
Heine, J ;
Buie, D ;
Johnson, DRE .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2000, 48 (03) :843-856
[7]   The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer [J].
Crane, CH ;
Skibber, JM ;
Birnbaum, EH ;
Feig, BW ;
Singh, AK ;
Delclos, ME ;
Lin, EH ;
Fleshman, JW ;
Thames, HD ;
Kodner, IJ ;
Lockett, MA ;
Picus, J ;
Phan, T ;
Chandra, A ;
Janjan, NA ;
Read, TE ;
Myerson, RJ .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2003, 57 (01) :84-89
[8]   Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer [J].
de Gramont, A ;
Figer, A ;
Seymour, M ;
Homerin, M ;
Hmissi, A ;
Cassidy, J ;
Boni, C ;
Cortes-Funes, H ;
Cervantes, A ;
Freyer, G ;
Papamichael, D ;
Le Bail, N ;
Louvet, C ;
Hendler, D ;
de Braud, F ;
Wilson, C ;
Morvan, F ;
Bonetti, A .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (16) :2938-2947
[9]  
DOUGLASS HO, 1986, NEW ENGL J MED, V315, P1294
[10]   PREOPERATIVE RADIOTHERAPY AS ADJUVANT TREATMENT IN RECTAL-CANCER - FINAL RESULTS OF A RANDOMIZED STUDY OF THE EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER (EORTC) [J].
GERARD, A ;
BUYSE, M ;
NORDLINGER, B ;
LOYGUE, J ;
PENE, F ;
KEMPF, P ;
BOSSET, JF ;
GIGNOUX, M ;
ARNAUD, JP ;
DESAIVE, C ;
DUEZ, N .
ANNALS OF SURGERY, 1988, 208 (05) :606-614