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Welcome to Dr. Hamid Sanatinia's Virtual Headquarters
Rectal Cancer

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Neoadjuvant
Adjuvant
Metastatic/Recurrent
Concurrent Chemoradiation
Xeloda & Radiation Therapy

Preoperative Regimen:
High-dose preoperative radiotherapy- 25 Gy in 5 fractions over 1 week.
Swedish Rectal Cancer Trial
NEJM 336:980-987, 1997

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Post-operative Regimen:

Concurrent Chemoradiation:


5FU 500 mg/m2/d rapid IV DAYS 1-5 & 36-40 & 450 mg/m2/d DAYS 134-138 & DAYS 169-173
Protracted 5FU 225 mg/m2/d by portable ambulatory infusion pump during the entire period of pelvic irradiation
PELVIC RADIATION 180 cGy over 5 weeks (total 4500 cGy) beginning on DAY 64

REF: NEJM 331:502, 1994. Improving Adjuvant Therapy for Rectal Cancer by Combining Protracted-Infusion Fluorouracil with Radiation Therapy after Curative Surgery
Compared to bolus injections of 5FU, the PVI group had a significant decrease in the overall rate of tumor relapse (from 47 to 37 percent, P = 0.01), distant metastasis (from 40 to 31%, P = 0.03),the time to relapse (P = 0.01) and survival (P = 0.005);their tumor-relapse rate was decreased by 27%, and their death rate by 31%
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***ADVANCED RECTAL CANCER

Chemoradiation:
May be used to convert fixed unresectable lesions into resectable lesions

5FU 200-250 mg/m2 delivered via a portable pump during pelvic radiation therapy
RADIATION 450 cGy over 5 weeks

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Xeloda with Radiation Therapy:
Xeloda 800 mg/m2 PO BID 5 days a week during ra

Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114.
Author: Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA
Source: J Clin Oncol; 15(5):2030-9 1997  UI: 9164215
Abstract: PURPOSE: The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole. METHODS: A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole. RESULTS: With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation. CONCLUSION: There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation

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Phase I Study of Capecitabine Combined with Simultaneous Radiotherapy Rectal Cancer.



Juergen Dunst et al. ASCO Abstract No 591-2001



Capecitabine (Xeloda) is an oral fluoropyrimidine which mimics continuous 5-FU-infusion and has demonstrated efficacy in a variety of tumors. The final conversion of the prodrug to 5-FU relies on thymidine phosphorylase (TP), which is present predominantly in malignant cells. Studies in human cancer xenograft models have shown that radiotherapy upregulates TP-activity in tumor but not in healthy tissue. In rectal cancer, concurrent radiation and 5-FU-chemotherapy is considered standard treatment for rectal cancer. We have therefore performed a phase I trial to determine the maximum tolerated dose of capecitabine in conjunction with simultaneous radiotherapy (five times weekly 1.8Gy to the pelvis, total dose 50.4Gy, boost of 5.4Gy in selected cases). Capecitabine was administered twice daily, with the first dose applied 2 hours before radiotherapy. To date, 36 patients (25 males, 11females; mean age: 65years) have been recruited at following dose levels: 2x250mg/m (n=3), 2x375mg/m(n=3), 2x500mg/m(n=6), 2x650mg/(n=6) 2x825mg/m (n=12) and 2x1000mg/m (n=6). Patients were treated for locally advanced disease in a neo-adjuvant setting (n=10), or after curative surgery (n=23) or with palliative intent (n=3). The most common toxicities (30 evaluable pats.) were mild to moderate leukopenia (53%), skin reactions in the radiation fields (43%), diarrhea (33%) and nausea (22%). The only grade 3/4 adverse reactions were skin toxicity (2x hand-foot-syndrome, 1x rash, 1x itch) and diarrhea (n=1). Dose-limiting toxicity (two cases with grade 3 hand-foot-syndrome) was reached at a level of 2x1000mg/m. 5/7 evaluable neo-adjuvant cases showed down-staging with one case of pCR at time of surgery. In summary, capecitabine can be safely administered concurrently with pelvic radiotherapy. The recommended dose level of 2x825mg/m daily is tested in an ongoing phase-II study.

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Publication Year: 2001



2165



 

Enhanced Tumoricidal Effect of Preoperative Chemoradiation Using Capecitabine for Locally Advanced Rectal Cancer.



Wan-Hee Yoon, et al ASCO Abstract 2165-2000



It was reported that radiation (RT) increased thymidine phosphorylase (TP) levels in tumors and combination of capecitabine enhanced antitumor effect in human colon cancer xenograft. The objective of this study was to evaluate whether the combination of capecitabine and RT can enhance antitumor effect compare to Mayo regimen in rectal cancer. Locally advanced mid or lower rectal cancer without distant metastasis were treated with preoperative chemoradiation (CXRT) using capecitabine (n=23) and conventional preoperative CXRT using Mayo regimen (n=44). RT was delivered to the whole pelvis at 45 Gy followed by a boost of 5.4 Gy to the primary tumor and concurrent chemotherapy of 2 cycles of capecitabine (2500 mg/day for 2 weeks) and leucovorin (30 mg/day, PO) was used. For Mayo regimen, 2 cycles of 5-FU (500 mg/m2/day, IV) and leucovorin (20 mg/m2/day, IV) were employed. Definitive surgery was performed 6 weeks following completion of preoperative CXRT. Pathologic complete response was achieved in 34.8% of capecitabine group, and in 4.5% of Mayo regimen group (p=0.007). The significant tumoricidal effect according to Ohboshi-Shimosato's classification ( grade IIb) was statistically more frequently found in capecitabine group compared to Mayo regimen group (60.9% vs 34%, respectively, p=0.003). The incidence of sphincter preservation for the tumor located less than 6 cm was significantly higher in capecitabine group (84.6% vs 40.7%, p=0.016). Downstaging of tumor depth and nodal status was frequently noted in capecitabine group (p=0.006 and p=0.13, respectively). In Mayo regimen group, grade 3-4 leukopenia (11.4%) and dermatitis (20.5%) were observed while such toxicities were not found but mild hand-foot syndrome (grade 1-2) was evident in 13% of capecitabine group. These results suggest that preoperative CXRT using capecitabine may be very safe, more tolerable and more effective neoadjuvant modality compare to Mayo regimen. (This work was supported in part by Roche Korea Co.)