Duration of adjuvant chemotherapy for breast cancer: a joint analysis of two randomised trials investigating three versus six courses of CMF

Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive ‘classical’ cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (±s.e.) were 54±2% for three cycles and 55±2% for six cycles (n=1024; risk ratio (risk ratio: CMF×3/CMF×6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Amyloidosis in Hodgkin's Disease

A patient with a 13-year history of Hodgkin's disease, who developed the terminal complication of amyloidosis manifesting in a nephrotic syndrome resulting in death, is reported. The incidence of this rare complication is reviewed from reports in the literature; to date only 53 unequivocal cases of amyloidosis, in association with Hodgkin's disease, have been described. The clinical picture is ciscussed, and the possible pathogenesis of amyloidosis is considered. The importance of intensive combination chemotherapy for preventing long-term complications, is stressed.S. Afr. Med. J., 47, 1 (1973)

Prognostic Factors for Survival in Hepatocellular Carcinoma

Associations between patient characteristics and survival were investigated in 432 patients with hepatocellular carcinoma. Those patients were prospectively studied by the Eastern Cooperative Oncology Group, and each had his or her diagnosis reconfirmed by a pathology review panel. There were 301 North American and 131 South African patients. Sixty-nine % of the North American patients and 82% of the South African patients were male. There were 187 Black patients, 62 of whom were from North America. The study population is unique among hepatocellular carcinoma patients in that eligibility, evaluability, and endpoint definitions were standardized, and patients from both North America and South Africa received similar treatments at a similar time. Factors with the most significant adverse effect on survival are impaired performance status, male sex, older age, and disease symptoms (jaundice and reduced appetite). There is no apparent difference in survival between White and Black patients within North America, but North American patients survived longer than South African patients. Among the different therapies, p.o. 5-fluorouracil was associated with the poorest median survival time (6 wk), and i.v. 5-fluorouracil plus semustine with the best median survival time (24 wk). © 1988, American Association for Cancer Research. All rights reserved

Chemically induced hair loss/alopecia

Increased shedding of hair and noticeable hair thinning or baldness (alopecia) are increasingly cited as side effects of exogenous chemicals/drugs. This chapter reviews some drugs implicated as well as mechanisms that may be responsible, describes criteria for defining the mechanism, and proposes animal and human assay models. This background provides the basis of similar judgment as relates to percutaneous penetration (and inhalation) of chemicals at the work site. Hair anatomy: Hair represents complete maturation of follicular matrical cells and is a fully cornified structure that emanates from a follicle and extends above the surface of the skin from varying distances. It has three components: an outer cuticle, a cortex, and an inner medulla. Hair grows in three phases: (1) growing or anagen, (2) involution or catagen, and (3) resting or telogen. Nonchemical-related hair loss: Few endogenous events affecting hair growth are delineated. Extreme starvation or protein deprivation may result in formation of sparse or brittle hair through diminished mitotic activity. Also major systemic insult, such as high fever, major surgery, illness, or trauma may result in hair follicles being thrown into an untimely telogen effluvium. Anagen versus telogen hair loss: Chemicals or medications may either cause excessive hair shedding by precipitating telogen development, directly poison the anagen root, or work in other undetermined ways. The phase of hair loss may be determined by examining the shed or easily plucked hair. Proving that alopecia in an individual is caused by a chemical/drug may be difficult; the most conclusive demonstration of chemical-/drug-related hair loss is reproduction of hair loss with repeated administration of the putative materials. However, the pathobiology of the response of the human hair follicle to chemotherapy is largely unknown. Hair loss is discussed in detail. Among the subjects of discussion are types of hair loss (e.g., anagen, medications precipitating telogen), chemicals causing hair loss (e.g., antimitotic agents, phenyl glycidyl ether), medications causing hair loss of unknown type (e.g., antithyroid drugs), medications possibly associated with hair loss, as well as chemically induced cosmetic alopecia, and typical scenarios in alleged occupational hair loss