| Disease | THE CURRENT INTENSE INTEREST IN TAXOL IS BASED ON PHASE I AND PHASE II TRIAL REPORTS OF ANTI-TUMOR ACTIVITY IN HUMANS, PARTICULARLY IN DRUG-REFRACTORY OVARIAN AND BREAST CARCINOMAS, NSCLC, AND MALIGNANT LYMPHOMAS. TAXOL HAS SHOWN SIGNIFICANT
ANTINEOPLASTIC ACTIVITY IN HEAVILY PRETREATED PATIENTS WITH ADVANCED, RELAPSED OR (PLATINUM-)REFRACTORY OVARIAN CANCER WITH RESPONSE RATES RANGING FROM 20 TO 50%. PHASE II STUDIES SHOWED RESPONSE RATES FROM 25 UP TO 62% IN PRETREATED PATIENTS
WITH METASTATIC BREAST CANCER, IN ADVANCED NON-SMALL CELL LUNG CANCER (STAGES IIIB AND IV) 21 UP TO 24%, IN HEAD AND NECK CANCER 37%, IN MALIGNANT LYMPHOMAS 25%. IN PHASE II TRIALS WITH PATIENTS WITH ADVANCED COLORECTAL, PROSTATE, RENAL CELL
CARCINOMA, AND PANCREAS CARCINOMA NO SIGNIFICANT ACTIVITY WAS SEEN. A BROAD PHASE II SCREENING IS NOT YET COMPLETED. PHASE I TRIALS OF TAXOL COMBINATIONS ARE ONGOING (WITH CARBOPLATIN, DOXORUBICIN, RADIOTHERAPY). THE RECOMMENDED INITIAL DOSE
FOR TAXOL IN PHASE II TRIALS WAS 135-250 MG/M2. PRELIMINARY DATA SUGGEST THAT LESS SIDE EFFECTS OCCURRED WHEN TAXOL WAS ADMINISTERED AS A 3-HOUR INFUSION COMPARED TO THE 24 HOUR INFUSION SCHEDULE. THE TOXICITY PROFILES WERE ACCEPTABLE AND
MANAGEABLE. THE DOSE-LIMITING TOXICITIES WERE BONE-MARROW SUPPRESSION, HYPERSENSITIVITY REACTIONS, AND NEUROTOXICITY. IMPORTANT QUESTIONS REGARDING OPTIMAL DOSE AND SCHEDULE, THE DEVELOPMENT OF TAXON COMBINATION CHEMOTHERAPY AND INTEGRATION
OF THIS AGENT INTO FIRST-LINE TREATMENT PROGRAMS PROVIDE THE CURRENT CHALLENGES. |