Enhanced antitumor activity of combination radioimmunotherapy ((131)I- labeled monoclonal antibody A33) with chemotherapy (Fluorouracil) Journal Article
| Authors: | Tschmelitsch, J.; Barendswaard, E.; Williams, C. Jr; Yao, T. J.; Cohen, A. M.; Old, L. J.; Welt, S. |
| Article Title: | Enhanced antitumor activity of combination radioimmunotherapy ((131)I- labeled monoclonal antibody A33) with chemotherapy (Fluorouracil) |
| Abstract: | Monoclonal antibody (mAb) A3 reacts with an antigen expressed by >95% of colon cancer and normal colon epithelial cells. An either Phase I trial of 131I-labeled mAb (131I-mAb A33) demonstrated bone marrow suppression as the dose-limiting toxicity, and although modest antitumor effects were seen, no normal colon toxicity was observed. In this study, a nude mouse model was used to test whether combinations of low-dose 131I-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitumor effects, compared to 131I-mAb A33 alone or either drug regimen alone. 5-FU was administered either at 30 mg/kg/day for 5 days or at 75 mg/kg/day on days 1 and 5. In assessing the reduction in tumor volumes over the first 28 days of the experiment. 5-FU treatment (with or without leucovorin) in combination with 131I-mAb A33 showed a statistically significant additive antitumor effect compared to 131I-mAb A33 alone or to chemotherapy alone. When long-term survival was used as an end point, 38% of the mice treated with 5-FU and 131I-mAb A33 were disease free at 276 days compared to none from other group, suggesting a synergistic effect. These data indicate that Phase II clinical trials combining radiolabeled antibody therapy with 5-FU-based treatments are warranted. |
| Keywords: | cancer chemotherapy; cancer survival; unclassified drug; human cell; doxorubicin; fluorouracil; dose response; drug potentiation; nonhuman; cancer radiotherapy; animals; mice; antimetabolites, antineoplastic; tumor volume; antineoplastic combined chemotherapy protocols; animal experiment; animal model; colonic neoplasms; antineoplastic activity; tumor xenograft; tumor cells, cultured; carmustine; time factors; antibodies, monoclonal; antigens, neoplasm; nude mouse; iodine radioisotopes; mice, nude; membrane glycoproteins; folinic acid; colon cancer; antineoplastic agents, alkylating; transplantation, heterologous; neoplasm transplantation; cancer control; antibiotics, antineoplastic; monoclonal antibody a33 i 131; radioimmunotherapy; leucovorin; low energy radiation; colon; antigen antibody reaction; humans; human; female; priority journal; article; monoclonal antibody a33 |
| Journal Title: | Cancer Research |
| Volume: | 57 |
| Issue: | 11 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1997-06-01 |
| Start Page: | 2181 |
| End Page: | 2186 |
| Language: | English |
| PUBMED: | 9187118 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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