No Increased Risk of Taxol Toxicity in Older Patients

To the Editor: Paclitaxel (Taxol®) is one of the first of a new category of anticancer drugs that promote and stabilize premature microtubule assembly. It is a new and promising drug in the treatment various solid tumors, particularly in ovarian and breast carcinoma.1 Activity has also been noted in non-small cell lung cancer and metastatic melanoma.2 These disorders, as well as most solid tumors, are diseases with a significant proportion of patients greater than 65 years of age. Potential toxicities are anaphylaxis, cardiac arrhythmias, and bone marrow suppression. These toxic reactions may result in the reluctance of physicians to use paclitaxel in older patients.2 The aging of the population focuses attention on the adequacy of cancer care administered to older patients. Patterns of care and treatment decisions change significantly with increasing patient age.3 Physicians may undertreat older patients with chemotherapy, or may be reluctant to refer older patients for treatment.4, 5 There are only a few studies addressing chemotherapy toxicity with age.6-13 A retrospective analysis was performed of the first 50 patients treated with paclitaxel at our institution. The patients were analyzed by age in two groups. In Group A patients were 65 years old or older and in group B patients were less than 65 years old. The review consisted of an analysis of observed toxicities. Toxicity grading was according to standard World Health Organization criteria. Patients were monitored during their infusions and were subsequently questioned about toxicities. Physical examinations and histories were performed approximately every 2 to 3 weeks. Paclitaxel was administered using a standard institutional guideline which included a regimen for prophylaxis against the acute hypersensitivity reaction.2 Only patients with a prior history of cardiac disease had cardiac monitoring. Patients characteristics are described in Table 1. All patients failed prior chemotherapy. Fifty-eight percent of the patients had refractory ovarian cancer, and an additional 16% had peritoneal carcinomatosis. These patients had all received prior therapy with Cisplatin. Forty-two patients received a dose of 135 mg/m2 over 24 hours, and eight patients received doses of 150–200 mg/m.2 Forty-four patients received 24-hour infusions, and six received 3-hour infusions. Table 2 summarizes the treatment and toxicity data. All patients experienced alopecia. The two age groups were comparable in terms of performance status and administered cycles. The data also shows that there was minimal toxicity overall and no significant difference in the toxicity between the two groups (P < .05). This analysis of patients receiving paclitaxel indicated that the older age group tolerated the therapy well, without serious side effects. This is particularly significant as the group studied were all previously exposed to chemotherapy and may have been expected to have had increased toxicity. It is possible that the retrospective nature of this study may have underestimated the frequency and degree of toxicity. However, all patients were treated by the same group of physicians and had frequent follow-up. It is unlikely that the serious problems (≥grade 3 toxicity) would have been overlooked. In addition, because of our inclination to treat older patients aggressively, selection bias did not significantly affect our data. A study from the National Cancer Institute on doses of paclitaxel of 250 mg/m2 showed older patients did not differ from younger patients with respect to dose intensity received, cycles of therapy, or occurrence of serious or mild toxicities. The results of our study have supported the observation that toxicity was acceptable through multiple cycles of therapy.14 It is imperative to expand our knowledge base in terms of tolerance of chemotherapy in older individuals so they may be treated safely and effectively. The higher incidence of comorbid medical conditions in older people may further complicate treatment and needs to be taken into consideration during future drug trials.15 The impression at our institution was that paclitaxel was a very acceptable therapy for the older patients. The elimination of paclitaxel from a treatment regimen based solely on the grounds of patient age is not justified. We have shown previously that cisplatin is also safe in a similar population.6 Therefore the cisplatin, or carboplatin-paclitaxel combination, should be considered in older women with newly diagnosed ovarian cancer.