Experiment 694298
Worktypes
Compounds isolated
Details
| Property | Value |
|---|---|
| Pharmacology | |
| Administration route | IV |
| Organism | Empty organism |
| Citation | PITOT,HC: MC ELROY JR,EA: REID,JM: WINDEBANK,AJ: SLOAN,JA: ERLICHMAN,C: BAGNIEWSKI,PG: WALKER,DL: RUBIN,J: GOLDBERG,RM: ADJEI,AA: AMES,MM:. (1999). PHASE I TRIAL OF DOLASTATIN-10 (NSC 376128) IN PATIENTS WITH ADVANCED SOLID TUMORS.. 5(2) |
| Amount utilized | |
| Compound isolated | |
| Disease | PHASE I CLINICAL TRIAL TO CHARACTERIZE THE MAXIMUM TOLERATED DOSE, PHARMACOKINETICS, AND BIOLOGICAL EFFECTS OF DOLA-10 IN PATIENTS WITH ADVANCED SOLID TUMORS. ESCALATING DOSES OF DOLA-10 WERE ADMINSITERED AS AN I.V. BOLUS EVERY DAYS, USING A MODIFIED FIBONACCI DOSE ESCALATION SCHEMA. PHARAMACOKINETIC STUDIES WERE PERFORMED WITH THE FIRST TREATMENT CYCLE. NEUROLOGICAL TESTING WAS PERFORMED ON EACH PATIENT PRIOR TO TREATMENT WITH DOLA-1O, AT 6 WEEKS AND AT STUDY TERMINATION. THIRY ELIGIBLE PATIENTS RECEIVED A TOTAL OF 94 CYCLES (MEDIAN, 2 CYCLES; MAXIMUM, 14 CYCLES) OF DOLA-10 AT DOSES RANGING FROM 65 TO 455 MU G/M2. DOSE-LIMITING TOXICITY OF GRANULOCYTOPENIA WAS SEEN AT 455 MU G/M2 FOR MINIMALLY PRETREATED PATIENTS (TWO OR FEWER PRIOR CHEMOTHERAPY REGIMENS) AND 325 MU G/M2 FOR HEAVILY PRETREATED PATIENTS (MORE THAN TWO PRIOR CHEMOTHERAPY REGIMENS). NONHEMATOLOGICAL TOXICITY WAS GENERALLY MILD. LOCAL IRRITATION AT THE DRUG INJECTION SITE WAS MILD AND NOT DOSE DEPENDENT. NINE PATIENTS DEVELOPED NEW OR INCREASED SYMPTOMS OF MILD PERIPHERAL SENSORY NEUROPATHY THAT WAS NOT DOSE LIMITING. THIS TOXICITY WAS MORE FREQUENT IN PATIENTS WITH PREEXISTING PERIPHERAL NEUROPATHIES. |
| Dose amount | VAR |
| Number | 2 |
| Qualitative result | EQUIVOCAL |
| Animal | HUMAN ADULT |
| Dose expression | DOSE |
| Gender | GIVEN TO BOTH SEXES |