Vinorelbine and infusional 5-fluorouracil in anthracycline and taxane pre-treated metastatic breast cancer.

AIMS: To evaluate the efficacy and toxicity of a combination of intravenous vinorelbine and 5-fluorouracil (5-FU) given by continuous infusion in the treatment of metastatic breast cancer previously treated with anthracyclines and taxanes. MATERIALS AND METHODS: Sixty-one patients with metastatic breast cancer were treated with intravenous vinorelbine 30 mg/m2 on days 1 and 8 of each 21-day cycle together with 5-FU 200 mg/m2/day by continuous infusion. All had previously been treated with an anthracycline and 41% had also been previously treated with a taxane. All had normal haematological, renal and hepatic function and all but three had an Eastern Cooperative Oncology Group performance score of 2 or better. RESULTS: The overall response rate by World Health Organization criteria was 46% (28 patients); excluding nine non-evaluable patients gave a response rate of 54%. In patients who had previously been treated with both an anthracycline and a taxane, a response rate of 50% was observed (12 of 24 patients). Severe toxicity was uncommon, as was toxicity attributable to infusional 5-FU. Myelosuppression was rarely severe, but was common and led to delay or dose reduction in 38% of treatments. Eleven patients (18%) were admitted with fever and/or neutropenia and one patient died. The median received dose intensity was vinorelbine 16 mg/m2/week and 5-FU 143 mg/m2/day. CONCLUSIONS: The combination of vinorelbine and infusional 5-FU is active in metastatic breast cancer, including in patients previously treated with an anthracycline and a taxane. Toxicity is generally manageable, but myelosuppression is significant at this dose regimen. Recommended doses for routine clinical use are 5-FU 200 mg/m2/day and intravenous vinorelbine 30 mg/m2 days 1 and 15 on a 28-day cycle.

Osteomalacia as a late metabolic complication of Ifosfamide chemotherapy in young adults: illustrative cases and review of the literature.

Purpose. Ifosfamide is a drug commonly used in the management of sarcomas and other solid tumours. One potential toxicity of its use is renal tubular damage, which can lead to skeletal abnormalities; rickets in children and osteomalacia in adults. We aimed to characterise this rare complication in adults. Patients. Three illustrative patient cases treated in our institution are presented. All were treated for sarcoma, and received varying doses of ifosfamide during their therapy. Methods. We performed a review of the literature on the renal tubular and skeletal complications of ifosfamide in adults. Papers were identified by searches of PubMed using the terms "osteomalacia," "nephrotoxicity," "Fanconi syndrome," "ifosfamide," and "chemotherapy" for articles published between 1970 and 2006. Additional papers were identified from review of references of relevant articles. Results. There are only four case reports of skeletal toxicity secondary to ifosfamide in adults; the majority of data refer to children. Risk factors for development of renal tubular dysfunction and osteodystrophy include platinum chemotherapy, increasing cumulative ifosfamide dose, and reduced nephron mass. The natural history of ifosfamide-induced renal damage is variable, dysfunction may not become apparent until some months after treatment, and may improve or worsen with time. Discussion. Ifosfamide-induced osteomalacia is seldom described in adults. Clinicians should be vigilant for its development, as timely intervention may minimise complications.

HER2-positive breast cancer brain metastases: multiple responses to systemic chemotherapy and trastuzumab--a case report.

Brain metastases from metastatic breast cancer typically occur in 10-15% of patients and are associated with survival of 3-6 months. Recent series have shown that women with HER2-positive metastatic breast cancer receiving the drug trastuzumab develop brain metastases more frequently than this, but also that continuation of trastuzumab after diagnosis of brain metastases in such patients is associated with extended survival. Authors have speculated that this is due to improved systemic control of disease; however, a possibility is that trastuzumab may have a beneficial effect on cerebral metastases themselves. We report the case of a woman with HER2-positive metastatic breast cancer who developed multiple brain metastases while on trastuzumab, in whom the addition of systemic chemotherapy to continued trastuzumab has produced multiple treatment responses associated with prolonged survival. This is the first report of its kind.

A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial.

BACKGROUND: To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer. PATIENTS AND METHODS: Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were randomised to receive pre-operative infusional 5-FU 200 mg/m(2) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2) intravenous (i.v.) bolus on day 1 and cisplatin 60 mg/m(2) i.v. bolus on day 1, both repeating 3-weekly (infusional ECisF), or conventional bolus doxorubicin 60 mg/m(2) i.v. on day 1 and cyclophosphamide 600 mg/m(2) i.v. on day 1, both repeating 3-weekly (AC), both schedules for six courses. Patients subsequently had local therapy (surgery or radiotherapy or both) and tamoxifen 20 mg orally daily as appropriate. RESULTS: The 5 year results for AC and infusional ECisF, respectively, were as follows: overall response, 75% and 77%; complete clinical remission, 31% and 34%; pathological complete remission (pathCR), 16% for both; and pathCR with residual ductal carcinoma in situ (DCIS), 25% and 24%. Mastectomy rates were 37% and 34%, respectively. Five-year overall survival was 74% for AC and 82% for infusional ECisF (hazard ratio 0.76, 95% confidence interval 0.51-1.13; P = 0.18). Both treatments were well tolerated. Grade III/IV lethargy, vomiting, alopecia and plantar-palmar erythema were significantly greater for infusional ECisF; grade III/IV leucopenia was significantly greater for AC. CONCLUSIONS: Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer; with a median 5 year follow-up, the infusion-based schedule shows a non-significant trend towards improved survival.