Dysphonia as an unusual toxic event of oxaliplatin-based chemotherapy.

Oxaliplatin is a new, third-generation platinum complex. It has a good safety profile characterized by low hematological-gastrointestinal toxicity. No significant nephro-ototoxicity has been observed. Acute peripheral neuropathy is a common event affecting, as grade 1 or 2, 85-95% of patients. Recently, data on dysphonia toxicity, after the administration of oxaliplatin, has been reported in literature. This toxicity with acute onset can be misunderstood if not carefully looked for. However, it is self-limiting and a non-permanent (grade 1-2) neurotoxic phenomenon, which impairs transiently the quality of life of a percentage of oxaliplatin-treated patients. We report our experience in consecutive patients affected by advanced colorectal cancer treated with oxaliplatin-based chemotherapy. Overall, we observed 13 (16%) cases of dysphonia out of 81 consecutive patients treated with oxaliplatin-based chemotherapy. This toxic effect was self-limiting and all patients recovered rapidly. Nonetheless, a deeper understanding of this phenomenon is essential to give correct information to the patients.

Ifosfamide in advanced/disseminated breast cancer.

Ifosfamide is an alkylating agent active in various tumor types including breast cancer. The availability of mesna (sodium 2-mercaptoethanesulfonate) has increased its safety, avoiding the main dose-limiting side effect, urotoxicity. Interesting activity as a single agent, with response rates ranging from 7 to 30%, is reported in pretreated patients; more attractive data derived from phase II studies on ifosfamide combined with drugs known to be active in advanced breast cancer show response rates always over 35%. This review has taken in consideration papers published after 1995 and available on PubMed medline: the data indicate a potential usefulness of ifosfamide in the clinical management of advanced breast cancer, even if the exact therapeutic role of the drug in this setting should be derived from randomized studies not yet available.

Ifosfamide in the adjuvant therapy of soft tissue sarcomas.

Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56-119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).