| Objective: To study the best effect of the sequence and interval of the combination of TOPO I inhibitors -10-hydroxycamptothecin (HCPT) and TOPO II inhibitors-adriamycin (ADM) in vitro , vivo and clinical observation.Methods: 1) MTT was used to evaluate the effect of HCPT and ADM interval (K 12, 24, 36, 48, 60, 72honthe growth of ovarian cancer cell (SK-O-V3). 2) Mouse implanted with murine sarcoma SI80 cell, administered by ip ofN.S, single HCPT (lOmg/kg), single ADM (5mg/kg) and HCPT followed by ADM after 0, 8, 12, 24, 72h were used. Days of survival and cured numbers were observed to give increase in life span (ILS) and curable rate. 3) We conducted a study of HCPT, THP-ADM and CBP given to untreated patients with advanced non-small-cell lung cancer (NSCLC). Simultaneous administration group of 20 patients was given HCPT 6mg/m2 ivgtt on day 1-5, THP-ADM 20mg/m2 iv on day 1-2, CBP 75mg/m2 iv on day 1-5 Sequential administration group of 50 patients was given HCPT 10 mg/m2 ivgtt on day 1 -3, ADM 20mg/m2 iv on day 4-5, CBP 75mg/m2 iv on day 1-5. rhG-CSF was given to all patients on day 7,9, 11 after chemotherapy. Seventy patientswere divided randomly into two groups, to evaluate the effect and toxicities of two groups.Results: Combined administration of HCPT and ADM showed: 1) HCPT\ ADM and experimental groups all showed the inhibition on SK-O-V3cell, the inhibitor rate of HCPT was 36.95% it was better than that of the simultaneous administration group was 33.43%, but they weren't significant (p > 0.05). Inhibitor rate of ADM was 22.62% below that of the simultaneous administration group, they were significant (p < 0.05). Inhibitor rate of ADM administered after a 12h drug-free interval since treatment with HCPT is 49.28%, was over that of the ADM administered after a 24h drug-free interval since treatment with HCPT, they weren't significant (p > 0.05), but its inhibitor rate better than other groups, they were significant (p < 0.05). Inhibitor rate of HCPT administered after a 12h drug-free interval since treatment with ADM is the best in every sequential administration group of HCPT administrated after ADM exposure, but its inhibitor rate compared to that of simultaneous administration and HCPT administered after a 24h drug-free interval since treatment with ADM, weren't significant (p > 0.05). The sequential administration of HCPT and ADM, the inhibitor rate of the groups of ADM administered after HCPT exposure was better than that of the groups HCPT administrated after ADM exposure, but their inhibitor rate of the groups of ADMadministered after a 12 24 72h drug-free interval since treatment with HCPT compared respectively to that of every corresponding groups of HCPT administrated after ADM exposure, they weren't significant (p > 0.05). 2) In vivo, life-time of single HCPT single ADM and the groups of sequential administration: life-time of single HCPT had been prolonged compared to control group, but they weren't significant (p > 0.05). Life-time of simultaneous administration group had been prolonged compared to single HCPT group , but they weren't significant (p > 0.05). Life-time of single ADM group had distinctly been prolonged compared to control group, they were significant (p < 0.05). Life-time of ADM administered after 8h drug-free interval since treatment HCPT was better than that of other sequential administration groups. LIS of every experimental group was better than control group, they were significant (p < 0.05). LIS of the simultaneous administration of HCPT and ADM was better than that of single HCPT and worse than that of single ADM. LIS of ADM administered after 8h drug-free interval since treatment HCPT 8h was 300%, the best of the three sequential administration groups, they were significant (p < 0.05). Curable rate of every experimental group was better than control group. Curable rate of ADM administered after 8h drug-free interval since treatment HCPT was the best, except HCPT group, they were significant (p < 0.05). 3) A total of 70 untreated patientswas regist... |
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