A phase I study to determine the safety, tolerability and maximum tolerated dose of green-lipped mussel (Perna canaliculus) lipid extract, in patients with advanced prostate and breast cancer.

BACKGROUND: This was a phase I trial to determine the maximum tolerated dose (MTD) of a marine lipid extract from the New Zealand green-lipped mussel (Perna canaliculus), as an inhibitor of 5- and 12-lipo-oxygenase enzymes, in patients with advanced breast and prostate cancers. PATIENTS AND METHODS: This was an open-labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily schedule, orally. Patients remained on study until disease progression or unacceptable toxicity. RESULTS: From December 1999 to May 2003, 17 patients were enrolled. Fifteen of them were male with advanced prostate cancer and two were female with advanced breast cancer. The median age of the patients was 74 years (range 56-85 years). Sixteen patients were assessable for adverse events and dose-limiting toxicity (DLT). Reason for withdrawal from the study included progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no objective tumour responses noted. CONCLUSIONS: GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.

Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study.

Cancer of unknown primary site (CUP) represents up to 5% of all cancer diagnoses and is associated with poor survival. We have performed a prospective multicentre phase 2 trial to evaluate efficacy and toxicity of the combination of gemcitabine (G) and carboplatin (C) for patients with CUP. Patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospectively designated investigation and who had ECOG performance status 0-2 were treated with G 1000 mg m(-2) intravenously (i.v.) days 1 and 8, and C AUC 5 i.v. on day 8 every 3 weeks to a maximum of nine cycles. The primary end points were response rate, and toxicity, with secondary end points of progression-free survival and overall survival. Fifty-one (23 male, 27 female) patients were enrolled (one patient ineligible), with a median age of 69 years (range 41-83 years). Fifty patients were evaluable for toxicity and 46 patients were evaluable for efficacy. The overall response rate to the GC regimen was 30.5%. With a median follow-up of 24 months, the median progression-free survival was 18 weeks (4.2 months) and the median overall survival was 34 weeks (7.8 months). The frequency of grade 3 or 4 toxicity was low. Nausea/vomiting was the most common side effect, but was usually only mild in severity. Uncomplicated neutropenia (14%), thrombocytopenia (10%) and anaemia (8%) were the most common causes of grade 3-4 toxicity. The regimen was very well tolerated, particularly in the elderly. The GC regimen is an active regimen in CUP with excellent tolerability and should be considered particularly for elderly patients with CUP.

Treatment of metastatic breast cancer with continuous infusional 5 fluorouracil.

BACKGROUND: Single agent continuous infusional 5 fluorouracil (CI-5FU) via a central venous catheter (CVC) is usually reserved for breast cancer patients who have previously failed one or more chemotherapy regimens. The patients are usually heavily pre-treated with later stage disease. Previously published studies of CI-5FU have reported response rates as high as 54%. It is considered an approach with an acceptable side effect profile in such patients. AIMS: To evaluate the efficacy and toxicity of CI-5FU in previously treated metastatic breast cancer. METHODS: A retrospective review of advanced breast cancer patients treated with CI-5FU between October 1992 and October 1996 was performed. Response to treatment, toxicity, CVC complications and patient survival were analysed. RESULTS: Twenty-four patients with metastatic breast cancer were treated with CI-5FU. All had received previous chemotherapy, including 19 patients (79%) with prior 5FU exposure and eight patients (33%) who had previous high dose chemotherapy with autologous stem cell transplantation. The median duration of CI-5FU treatment was 3.1 months. Nineteen patients had evaluable disease, three (16%) of whom demonstrated a partial response and four patients had stable disease. There were no complete responses. All responses occurred in soft tissue sites with no objective evidence of response in liver or bone metastases. The survival rate at one year was 21% (five of 24) and the median survival of all patients was 6.1 months. Five patients (21%) stopped treatment due to treatment related morbidity (two CVC complications and three CI-5FU side effects). Diarrhoea, nausea, and palmar-plantar erythrodysaesthesia were the major side effects of chemotherapy. CVC complications requiring intervention, the most notable of which were infection and thrombosis, occurred in 11 patients (46%). There were no treatment related deaths. CONCLUSIONS: Single agent CI-5FU has modest activity in women with previously treated advanced breast cancer. The efficacy is lower than in previously published series. This may reflect patient selection factors. The toxicity was mainly related to CVC complications. Important issues relating to quality of life need to be objectively measured in future studies of CI-5FU.

Rifampicin as treatment for pruritus in malignant cholestasis.

The efficacy and safety of using rifampicin to treat the pruritus associated with malignant cholestasis was evaluated. The outcomes of eight patients who received 150 mg rifampicin twice daily were reviewed. All responded, with six having complete resolution of the itch. Two patients were able to discontinue rifampicin following resolution of their cholestatic jaundice by surgery and chemotherapy respectively. No side effects were reported. Rifampicin is a safe effective treatment for the pruritus associated with cholestasis secondary to cancer.