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Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.

The objective of this study was to examine the feasibility, implementation, acceptability and impact of an evidence-based specialist breast care nurse (SBN) model of care in Australia. Primary data were collected from four diverse Australian breast cancer treatment centres over a 12-month period. The design was a multicentre demonstration project. Information about the provision of care and patient needs was collected through prospective logs. Structured interviews were conducted with women who received the SBN intervention (N = 167) and with a control group of women treated prior to the intervention period (N = 133). Health professionals (N = 47) were interviewed about their experience of the SBN. Almost all women had contact with an SBN at five scheduled consultations and 67% of women in the intervention group requested at least one additional consultation with the SBN. Women in the intervention group were more likely to receive hospital fact sheets and to be told about and participate in clinical trials. Ninety-eight per cent of women reported that the availability of an SBN would affect their choice of hospital, with 48% indicating that they would recommend only a hospital with a SBN available. Health professionals reported that SBNs improved continuity of care, information and support for the women, and resulted in more appropriate referrals and use of the time of other members of the team. In conclusion, the SBN model is feasible and acceptable within diverse Australian treatment centres; there is evidence that some aspects of care were improved by the SBN.

Summary: Cyclophosphamide was given to a young woman with nephrotic syndrome, and was inadvertently continued until the eighth week of her pregnancy. The baby had only two minor malformations; an umbilical hernia and a cutaneous haemangioma, which were probably not due to the cyclophosphamide.

Protection against experimental autoimmune encephalomyelitis (EAE) was studied in the guinea pig and the Lewis rat. Basic protein of myelin (BPM) injected in incomplete Freund's adjuvant (IFA) gave solid protection against subsequent challenge with normally encephalitogenic doses of BPM in complete Freund's adjuvant (CFA). Protection depended on the amount of BPM in IFA injected and on the duration of the interval between protection and encephalitogenic challenge with BPM in CFA. Notably, protection was long lasting; it remained demonstrable, to some degree for 52 weeks in guinea pig and 32 weeks in rats, these being the longest intervals tested. Protection could not be correlated with serum antibody levels to BPM, and was afforded in the guinea pig by the injection, in IFA, of a synthetic peptide matching residues 112–122 of human BPM; this peptide produced no detectable serum antibody to BPM. Protected guinea pigs had intact cell-mediated immunity to BPM, as measured by inhibition of macrophage migration in vitro. The mechanism of protection may involve the production, following injection of BPM in IFA, of a class of suppressor thymic lymphocytes capable of overriding otherwise encephalitogenic thymic lymphocytes.

Human malignant melanoma cell lines established in tissue culture were successfully transplanted sc into BALB/c nude mice. The growth rate of the resulting tumors was significantly suppressed when lymphocytes from the patient in whom the tumor arose were injected iv into BALB/c nude mice at the same time as sc tumor transplantation, but inoculation with lymphocytes from a person without a tumor was ineffective. Cell separation identified T-lymphocytes as the active subpopulation. Growth of the tumors was also significantly suppressed by reconstitution of the mice with normal BALB/c lymphocytes; lymphocytes from BALB/c mice previously immunized against the melanoma line were not more effective than nonimmune lymphocytes in preventing tumor growth. Sera from normal BALB/c mice or BALB/c mice immunized against a human melanoma cell line effectively suppressed growth of that cell line in BALB/c nude mice if given at the time of tumor transplant. The results suggested that, whereas murine lymphocytes reconstitute the ability of nude mice to react to xenogeneic antigens on the human tumor, human lymphocytes showed greater specificity to autologous human melanoma-associated antigens.

Carcinoembryonic antigen (CEA) was estimated in plasma from 70 patients with a renal transplant, 105 patients with glomerulonephritis who had received immunosuppressive therapy, and 124 healthy controls. There were raised levels in 30% of those with a renal transplant, 10% of those with glomerulonephritis and 2% of controls, and levels were higher in current smokers. CEA levels did not correlate with pre-transplant dialysis time nor with serum creatinine levels, but tended to fall with increasing time after transplantation, especially in non-smokers. CEA levels did not correlate with prednisolone dosage nor with number of rejection episodes, after allowing for time after transplantation and smoking habit. Nine of 70 patients with a renal transplant and three of 105 with glomerulonephritis had cancer, of skin in seven, cervix uteri in four, and colon in one. CEA was raised in all four transplant recipients with a visceral cancer (cervix three and colon one), but in none of the five with cutaneous cancer. Raised CEA levels occurring late after a renal allograft should prompt a careful search for visceral cancer.

Summary: In 14 patients with multiple sclerosis, cell-mediated immunity to the basic protein of human myelin (BPM) was measured by lymphocyte transformation with incorporation of tritiated thymidine. Other patients studied included those with cerebrovascular accident, and various control groups. No transformation response of lymphocytes to BPM was observed in patients with multiple sclerosis, in the active or interval phase. However, significant transformation (p < 0.05) was detected in patients with brain damage due to cerebrovascular accident. Thus lymphocyte reactivity to BPM can be induced by brain damage associated with strokes, but could not be shown to be an immunological feature of multiple sclerosis.

Cytotoxic therapy is regarded with grave distrust by many patients, and also by a substantial number of doctors. The side effects of such therapy are real and may be severe, but they are by no means uniform in severity. Unfortunately, people often assume the worst possible side effects when decisions about chemotherapy are made. Discussion of the effects to be expected usually need to be repeated in order to overcome the communication difficulties common in patients newly aware of their diagnosis or of disease recurrence. Group discussions with other patients may also be useful, as they are in other aspects of coping with cancer (1).