GESTATIONAL TROPHOBLASTIC TUMORS - CYTOSTATIC TREATMENT RESPONSE EVALUATED FROM HCG MODELING

Fifty-eight patients representing with gestational trophoblastic tumors were treated at the department of Gynaecologic Oncology of the Norwegian Radium Hospital during the period from 1977 to 1990. Individual serial measurements of hCG were analyzed applying a mathematical dynamic tumor marker model. Fifty-three low-median risk patients were given standard cytotoxic chemotherapy with a methotrexate-actinomycin regimen. The surving fraction of hCG-producing cells following the first chemotherapy cycle decreased exponentially with methotrexate dose. The estimated surviving fraction of hCG-producing cells was not a prognostic factor in those patients who needed second-line chemotherapy. These patients, however, were characterized by high pre-treatment hCG levels and rapid proliferation of hCG-producing cells. Five patients, three high risk and two medium risk, were allocated to a high dose methotrexate regimen. Surviving fractions of hCG-producing cells in high dose methotrexate were a factor of 3-10 times lower than the surviving cell fractions in the low dose regimen, indicating a biphasic dose-response relation for methotrexate. Medium risk patients were found to have an unacceptably high recurrence rate after methotrexate actinomycin-D therapy and should be treated with more intensive chemotherapy. It is recommended that drug dose should be corrected for body-volume in low risk regimes, to avoid drug resistance developing because of increased treatment time.