Acute toxicity of neoadjuvant bolus 5-FU/methotrexate and leucovorin rescue followed by continuous infusion 5-FU plus pre-operative radiation therapy for rectal cancer Journal Article


Authors: Minsky, B. D.; Conti, J.; Cohen, A. M.; Kelsen, D. P.; Saltz, L.; Guillem, J. G.; Paty, P. P.; Bass, J.; Bertino, J. R.
Article Title: Acute toxicity of neoadjuvant bolus 5-FU/methotrexate and leucovorin rescue followed by continuous infusion 5-FU plus pre-operative radiation therapy for rectal cancer
Abstract: We present an analysis of acute toxicity of 3 cycles of neoadjuvant bolus methotrexate (MTX) with leucovorin (LV) rescue plus bolus 5-FU, followed by continuous infusion 5-FU with concurrent pre-operative 5040 cGy, and post-operative bolus 5-FU/LV in patients with rectal cancer. Nine patients (1: unresectable, 6: locally advanced, 2: resectable but bulky disease) with adenocarcinoma of the rectum limited to the pelvis were enrolled. For the neoadjuvant segment, the first 4 patients received 3 successive weeks of chemotherapy followed by a 1 week break (continuous course). Due to toxicity, the remaining 5 patients received an intermittent treatment schedule consisting of 3 weekly cycles with 1 week break between cycles 1 and 2 and cycles 2 and 3 followed by a 1 week break (intermittent course). The complete response rates were clinical: 11%, pathologic: 11%, and total: 22%. The incidence of total Grade 3+ toxicity during the neoadjuvant chemotherapy segment was 56% (5/9), and during the pre-operative combined modality segment was 33% (3/9). Therefore, for the entire pre-operative period (neoadjuvant chemotherapy plus pre-operative combined modality segments) 67% (6/9) patients had grade 3+ toxicity. The incidence of total Grade 3+ toxicity during the post-operative combined modality segment was 50% (3/6). The preliminary data suggest that resectability and complete response rates with this neoadjuvant MTX/5-FU/LV plus pre-operative radiation therapy and continuous infusion 5-FU regimen are similar to our prior experience with conventional bolus 5-FU/LV and radiation therapy. However, the incidence of grade 3+ acute toxicity is higher. Additional experience is needed to determine if this approach offers a significant advantage in local control and survival.
Keywords: adult; clinical article; treatment outcome; aged; clinical trial; fluorouracil; cancer combination chemotherapy; neoadjuvant therapy; methotrexate; bolus injection; phase 2 clinical trial; continuous infusion; gastrointestinal toxicity; folinic acid; phase 1 clinical trial; rectum carcinoma; intravenous drug administration; rectum resection; rectal cancer; oral drug administration; preoperative radiotherapy; human; male; female; priority journal; article; pre-operative therapy
Journal Title: Radiation Oncology Investigations
Volume: 4
Issue: 2
ISSN: 1065-7541
Publisher: John Wiley & Sons  
Date Published: 1996-01-01
Start Page: 90
End Page: 97
Language: English
DOI: 10.1002/(sici)1520-6823(1996)4:2<90::aid-roi7>3.0.co;2-g
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Leonard B Saltz
    580 Saltz
  2. Philip B Paty
    367 Paty
  3. Bruce Minsky
    258 Minsky
  4. Joseph Bertino
    257 Bertino
  5. Jose Guillem
    364 Guillem
  6. Alfred M Cohen
    165 Cohen
  7. David P Kelsen
    332 Kelsen