Studies on chemotherapy for malignant lymphoma Part 2. Evaluation of anticancer drug combination on hematologic malignant cell lines using median effect analysis

To establish an effective combination chemotherapy for hematologic malignancies, the combined effects of four anthracycline-anthraquinones and five other drugs were assessed in vitro. The anthracycline-anthraquinones were adriamycin (ADM), aclarubicin (ACR), THP-adriamycin (THP-ADM), mitoxantrone (MXT) and five other drugs were 4-hydroperoxycyclophosphamide (4HO(2)-CTX), cytarabine (Ara-C), vincristine (VCR), etoposide (ETP), cisplatin (CDDP). Median effect analysis presented by Chou and Talalay was used to assess the combined effects of these drugs on two cell lines (HL-60 and Raji). In addition, the ratio of maximal tolerable dose (MTD) to the dose that produced 50% growth inhibition (Dm) was calculated to estimate the clinical activity of each drug. Data of MTD/Dm indicated that THP-ADM and MXT might be clinically superior to ADM and ACR. The results of median effect analysis shown by a combination index were as follows : As to HL-60 cells that were derived from acute promyelocytic leukemia cells, synergistic effects were seen in the combination of ACR and Ara-C, THP-ADM and CDDP, MXT and 4HO2-CTX, MXT and Ara-C, MXT and VCR, MXT and ETP, indicating that MXT showed efficient synergistic effects when combined with other drugs. As to Raji cells that were derived from Burkitt's lymphoma cells, synergistic effects were observed in the combinations of ADM and ETP, ADM and CDDP, ACR and VCR,THP-ADM and VCR, THP-ADM and ETP, THP-ADM and CDDP, MXT and VCR, indicating that THP-ADM showed efficient synergistic effects when combined with other drugs.

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