Synergistic effect of Taxol and additive effect of Avastin when combined with radioimmunotherapy

Objectives To investigate the effect of Taxol and Avastin on the therapeutic efficacy of Y-90-labeled B3 mAb, directed against Lewis Y antigen, in the treatment of Lewis Y-positive A431 tumors.

Methods Groups of nude mice (n = 5-9 mice/group) were inoculated s.c. with A431 tumor cells expressing Lewis Y antigen in the right hind flank. When the tumor size reached ~200 mm3, the mice received i.v. Y-90-labeled B3 alone (60 μCi/150 μg B3), i.p. Taxol alone (40 μg/kg), i.v. Avastin alone (5 mg/kg), two agents together (Y-90-B3 and 24 hr later, Taxol; or Avastin and 24 hr later, Y-90-B3), three agents together (Avastin, Y-90-B3, and Taxol at 1 day intervals), or no treatment. The tumor volume and the body weight were measured daily for the first 7 days and thereafter, two or three times a week. Mice were euthanized when the tumor size was 2 cm in diameter.

Results The control mice had a median survival time of 5 days. Taxol alone, Y-90-B3 alone, and Avastin alone delayed tumor growth with a median survival time of 17, 18, and 9 days, respectively. The combined therapy of Avastin with Y-90-B3 and Avastin with Taxol produced a modest increase of the median survival time to 20 or 18 days, respectively. The combined therapy involving Y-90-B3 with Taxol showed a striking synergistic effect in shrinking tumors and prolonging the survival time; on day 120, 3 of 9 mice (33%) treated with the combined therapy involving Y-90-B3 and Taxol were alive without tumor. The addition of Avastin before Y-90-B3 and Taxol produced a modest increase in the survival rate with 3 of 6 (50%) alive without tumor on day 120.

Conclusions There is a striking synergy when Taxol and radioimmunotherapy with Y-90-B3 are combined and the addition of Avastin further increases the therapeutic effect