Multigene expression profile testing in breast cancer: is there a role for family physicians?

BACKGROUND: Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. METHODS: We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. RESULTS: The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.

Phase II study of weekly edatrexate as first-line chemotherapy for metastatic breast cancer: a National Cancer Institute of Canada Clinical Trials Group study.

PURPOSE: The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study to assess the efficacy and toxicity of edatrexate, a folate antagonist, in 35 patients with metastatic breast cancer. PATIENTS AND METHODS: The planned dose of edatrexate was 80 mg/m2/wk administered intravenously as first-line therapy. Prior adjuvant chemotherapy was allowed provided at least 12 months had elapsed from the completion of treatment to the development of recurrence. RESULTS: Mucositis was the dose-limiting toxicity in 34 assessable patients, resulting in a mean delivered dose-intensity of 57 mg/m2/wk. Other toxicities included myelosuppression, rash, pneumonitis, and increased AST. Side effects were generally mild to moderate. The complete plus partial remission rate (13 patients; 41%) was impressive. CONCLUSION: Edatrexate is an active agent against metastatic breast cancer, with acceptable toxicity. A lower than planned delivered dose-intensity was mainly due to mucositis.

Successful re-treatment with taxol after major hypersensitivity reactions.

PURPOSE: To describe the successful re-treatment of eight patients who had major hypersensitivity reactions (HSRs) to taxol and to suggest a regimen for re-treating patients who develop major HSRs. PATIENTS AND METHODS: The treatment courses of eight patients who developed major HSRs and were rechallenged with taxol were reviewed. Patients in this report represent all patients who are known to have been rechallenged with taxol after major HSRs. RESULTS: The most common approach used to rechallenge patients consisted of premedication with multiple high doses of corticosteroids and H1- and H2-histamine antagonists followed by the initiation of the taxol infusion at a reduced rate. All patients who experienced major HSRs were rechallenged successfully. After the rechallenge, these patients received 32 additional courses of taxol without HSRs. CONCLUSION: Re-treatment with taxol after major HSRs is feasible using multiple high doses of corticosteroids and antihistamine premedications and a reduced taxol infusion rate under close supervision. This approach may represent a valid alternative to the termination of taxol; however, a prospective evaluation is required to determine the true efficacy of this approach.

Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE: The National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of docetaxel as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS: Fifty-one patients with measurable MBC were studied. Three patients were ineligible and were excluded from analysis. The planned dose of docetaxel was 100 mg/m2 intravenously (i.v.) every 3 weeks. Prior adjuvant chemotherapy was allowed if at least 12 months had elapsed from completion of treatment to recurrence. RESULTS: The most severe toxicity was granulocytopenia. Ten patients (20.8%) were hospitalized for febrile neutropenia. The protocol was amended to a starting dose of 75 mg/m2 for the last 16 patients. Sixty percent of patients experienced hypersensitivity reactions (HSRs). After two protocol amendments, the use of a premedication regimen of oral dexamethasone and i.v. H1 and H2 blockers prevented significant HSRs. Edema developed in 62% of patients and was cumulative, was present in 50% who received greater than 400 mg/m2, and was not improved by premedication regimens. Following an independent radiology review, 22 partial remissions and four complete responses in 47 assessable patients were confirmed (response rate, 55%; 95% confidence interval [CI], 40% to 69%). The response rate for 15 assessable patients registered at 75 mg/m2 was 40% (95% CI, 16% to 67%); for 32 assessable patients registered at 100 mg/m2, the response rate was 63%, (95% CI, 43% to 78%). CONCLUSION: Docetaxel is an active agent in MBC. Its activity as a single agent is comparable to many combination chemotherapy regimens and is not affected by prior adjuvant chemotherapy. Studies are ongoing to improve its therapeutic index and to incorporate docetaxel in combination chemotherapy regimens.