No abstract

Paclitaxel is highly active against a variety of solid tumors including breast lung, ovarian and head and neck cancer. Although peripheral neurotoxicity is well-known side effect, central nervous system (CNS) toxicity-related standard dose of paclitaxel is extremely uncommon, because paclitaxel dose not cross the blood-brain barrier and is not detectable in the cerebrospinal fluid. We present a patient with advanced stage breast carcinoma who developed acute and spontaneous resolving encephalopathy after weekly dose of paclitaxel. The patient did not have brain metastasis, or prior whole-brain irradiation, or any type of neurosurgery. Radiological imaging studies showed no abnormalities. CNS toxicity of paclitaxel should be kept in mind in patients without a previous history of brain metastasis or brain irradiation and even with low weekly doses.

Docetaxel (Taxotere) and doxorubicin have previously demonstrated a significant antitumor activity in patients with metastatic breast cancer. Furthermore, a lack of cross resistance and overlapping toxicities between the two agents have been reported. In a prospective study, docetaxel (80 mg/m2, 1-hr iv infusion) and doxorubicin (60 mg/m2, 1-hr iv infusion) were administered as first-line chemotherapy in metastatic breast cancer patients to evaluate the clinical efficacy and toxicity of the combination. Forty-three patients were enrolled in the study. The median age was 47 years (range, 30-69). The docetaxel-doxorubicin combination was applied with 3-week intervals until progression. Complete response was achieved in 9 (21.4%) of 42 assessable patients and partial response in 24 (57.2%) patients, for an overall response rate of 78.6%. Median response duration was 8 months (3-18 months). Nausea and vomiting (76%), alopecia (64%), neutropenia (35.7%) and mucositis (33%) were the major side effects of the combination. There was one case of cardiac toxicity. In conclusion, the docetaxel-doxorubicin protocol can be considered as an active regimen for the treatment of patients with metastatic breast cancer with acceptable toxicity and a fairly high response rate.

Cyclophosphamide (CPA) and adriamycin (ADR) are widely used drugs for cancer chemotherapy. It has been reported that CPA and ADR singly or in combination could alter activities of a variety of drug-metabolizing enzymes in animals via multiple mechanisms. However, the effects of CPA/ADR on drug metabolism are largely unknown in human beings. Losartan metabolism has been suggested as a marker for determination of CYP2C9 activity. Caffeine is a commonly used probe to assess the metabolic activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO). The present study was designed to analyze the effects of CPA/ADR on these drug-metabolizing enzymes by using losartan and caffeine as probe drugs. A single oral dose of 25 mg losartan and a cup of instant coffee was given to 15 breast cancer patients on three occasions (before, and 2-4 h and 3 weeks after the adjuvant CPA/ADR chemotherapy [600 mg CPA/m2/day, 60 mg ADR/m2/day]). Losartan, caffeine and their metabolites were analyzed by using high-pressure liquid chromatography. When compared with baseline, CYP1A2 activity was increased by 20% and CYP2C9 activity was decreased by 315% 3 weeks after the administration of CPA/ADR chemotherapy (p = 0.05). The chemotherapy did not change the activities of CYP2A6, NAT2 or XO. CPA/ADR treatment caused a differential effect on drug-metabolizing enzyme activities, and this may contribute to predicting the efficacy and toxicity of chemotherapeutics, as well as understanding the drug-drug interactions.

Background: We have evaluated the clinical efficacy and toxicity of a modified etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) chemotherapy regimen that has been used by the Hacettepe University Department of Medical Oncology (Ankara, Turkey) since 1993. Methods: Thirty-two patients (18 men and 14 women) with refractory or recurrent non-Hodgkin’s lymphoma (NHL) were treated with this protocol. The median age of the patients was 39 years (range 21–66 years). Patients were hospitalized during therapy. On the first day, 2 g/m² cytarabine was given, followed on days 2–5 by 60 mg/m² etoposide, 500 mg of methylprednisolone and 25 mg/m² cisplatin. After two cycles of chemotherapy, clinical efficacy was assessed by clinical examination, chest radiography, ultrasonography and/or computed tomography. The complications were assessed on the basis of the World Health Organization criteria. Results: Nine patients (28%) had a complete response and 8 patients (25%) had a partial response. In responders, the median duration of remission was 6 months. By the end of the first year, 27% of the patients were still disease free and 66% were alive. High serum levels of lactate dehydrogenase had an adverse effect on disease-free survival, but no effect on overall survival (OS). The only unfavorable prognostic factor for OS was the presence of bulky disease. Neutropenia developed in 59% of patients, and febrile neutropenia developed in 74% of these patients, requiring hospitalization for an average of 8 days. Three patients died of neutropenia-associated sepsis despite broad-spectrum antibacterial and antifungal treatment. Thrombocytopenia was detected in 10 patients and anemia in 3 patients; among these, 7 patients with thrombocytopenia and 1 patient with anemia required transfusions. Conclusions: The modified ESHAP regimen induced remission in more than half of the patients with refractory or recurrent NHL. However, the duration of remission was brief. Moreover, significant myelotoxicity was common, and the risk of treatment-related death was 9%.