EVALUATION OF OCULAR SAFETY - TIRAPAZAMINE PLUS CISPLATIN IN PATIENTSWITH METASTATIC MELANOMAS

Ninety-six patients with metastatic melanoma treated with two consecut ive tirapazamine-cisplatin combination chemotherapy regimens were foll owed for signs of therapy-related ocular toxicity. Baseline and follow -up data were obtained such that each patient acted as his own control . A battery of vision-related tests was performed. These included: bes t corrected visual acuity, color vision, retinal fundus examination an d electro-oculograms (EOG), A brief health-related quality of vision t est was administered at each follow-up visit to detect and evaluate se lf-perceived changes in visual status. In the first study, 48 patients received i.v. tirapazamine over 2 h at 260 mg/m(2) (group 1) while in the second study 48 patients (group 2) received i.v. tirapazamine at 390 mg/m(2). Visual system assessment was conducted at three timepoint s: first at baseline, then at 6 weeks post-baseline, i.e. after two co urses of chemotherapy and visit two upon discontinuation of therapy. T here was no difference in visual acuity between group 1 and group 2 at baseline, followup 1 or at follow-up 2. Grouped data indicate that vi sual acuity was not affected by either dosage of chemotherapy. Group 1 at baseline found 15% below the normal EOG cutoff point, increasing t o 23% at follow-up 1 and increasing at follow-up visit 2 to 33%, Group 2 demonstrated the same EOG findings, but the results were more magni fied: baseline, 24%; follow-up 1, 44%; and follow-up 2, 44%. After eli minating those with abnormal color vision baselines, 21% (nine of 42) group 1 patients demonstrated abnormal color vision total error scores at follow-up 1 and 16.7% (four of 24) at follow-up 2. Few individuals showed changes in the higher dosage group. With the exception of one person in each dosage group, all changes were along the blue-yellow (t ritan) axis, which is associated with acquired color defects. Of 96 pa tients examined, proven fundus changes were found in only four subject s. These fundus findings included retinal hemorrhages, retinal nerve f iber layer infarcts (cotton wool spots) and small retinal pigment epit helium detachments. There was no systematic statistical significant di fference among the various measures of visual system outcome between g roups or test times. Data from all tests for individual patients in bo th groups reveals a sporadic distribution of changes in visual system tests. If toxicity were pronounced, one would expect consistency in th e findings and all or most of the assessment tests would be abnormal f or a particular patient. However, patients who were abnormal on one me asure of acuity were not necessarily abnormal on the other measures. [ (C) 1998 Lippincott-Raven Publishers.].