Sistema Peruano de Información Jurídica
RESOLUCION DIRECTORAL Nº 002-2012-PRODUCE-DGCHI
Nausea, vomiting, tiredness and alopecia are the side effects most frequently associated with cytotoxic therapy.318 Newer anti-emetics have reduced the severity of nausea and vomiting.319,320
Temporary alopecia sufficient to require a wig is common following
anthracyclines,321although less common in women having CMF.322Alopecia may be very distressing for the woman and her family, as it is a highly visible reminder of the cancer for which she is being treated. Although hair usually grows back within three months of completing treatment, it may have a different texture and be curlier than before.
Chemotherapy has been associated with long-term impairment in sexual function and infertility associated with premature menopause323,324 (Level III), with studies reporting between 50–60 per cent of women treated for early breast cancer having sexual dysfunction beyond 12 months post-treatment.325,326The causes of this may be direct, through gonadal and hormonal effects, and indirect, through fatigue, apathy, nausea, vomiting and sleep or appetite disturbances that interfere with libido.327 Change in sexual function is more evident in those women who become menopausal following chemotherapy,323 and this is a concern raised by women.328
Tiredness is another side-effect that may undermine the woman’s ability to cope with family and other responsibilities, particularly if it persists after completion of chemotherapy. Another source of concern for women is the subjective sense of impaired thinking and poor concentration following chemotherapy. There is limited research in this area, but one study reported cognitive impairment in 75 per cent of women who had completed 3–18 months treatment with CMF, CAF or tamoxifen.329 High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy.330Another study found that patients with breast cancer treated with adjuvant CMF have a significantly higher risk of late cognitive impairment than breast cancer patients not treated with chemotherapy.331These effects included problems with concentration and with memory.
Less common short-term side effects include mucositis, diarrhoea, conjunctivitis, chemical cystitis and anxiety about attending for treatment. Rarer side effects include febrile neutropenia, infection, venous thromboembolism and
haemorrhage.318
In the longer term, therapy-induced leukaemia is rare.332 The risk of death from adjuvant chemotherapy is very low.
Congestive cardiac failure is associated with higher cumulative doses of anthracyclines such as those of >500mg/m2 of doxorubicin or >900mg/m2 of epirubicin. It may be exacerbated by radiation therapy which includes the heart.
It is important that women should be fully informed of the short- and long-term effects of cytotoxic chemotherapy and of these potential side effects, including impact on body image and sexuality (Level III),333as well as of the potential benefits of treatment. The provision of information on treatment and treatment side effects improves emotional wellbeing (Level I).120
For information on menopausal symptoms see Menopause and hormone
replacement therapy: a booklet for women,1996 NHMRC and Hormone
replacement therapy for peri- and post-menopausal women: booklet for health professionals 1996, NHMRC.
Guideline Level of Reference
evidence
Women should be fully informed of the short- and III 333 long-term effects of cytotoxic chemotherapy on
general functioning and on body image, sexuality and fertility.
6 . 3 T A M OX I F E N
In the most recent Oxford overview,297 tamoxifen was associated with a highly significant improvement in recurrence-free survival in women with ER-positive tumours. It was recognised that tamoxifen had little benefit in patients with ER- negative tumours. Analysis was therefore confined to those women whose tumours were ER-positive or unknown.
The magnitude of the benefit of tamoxifen was clearly dependent on the duration of adjuvant tamoxifen therapy, as shown in Table 3.
As with cytotoxic therapy, the main divergence in recurrence-free survival was in the first five years, while overall survival advantages continued to accrue during the second five years.
Table 3: Tamoxifen duration: effect on outcome
Tamoxifen duration Recurrence-free survival Overall survival
Risk reduction Absolute % Risk reduction Absolute
% difference at 10 yrs % difference at 10 yrs
Node negative ~ 1 year 17 ± 8 4.7 13 ± 8 3.4 ~ 2 years 28 ± 5 5.6 11 ± 6 2.2 ~ 5 years 49 ± 4 14.9 25 ± 5 5.5 Node positive ~ 1 year 21 ± 3 7.5 12 ± 4 4.5 ~ 2 years 30 ± 3 10.0 19 ± 3 7.2 ~ 5 years 43 ± 5 15.2 28 ± 6 10.9
Data from Early Breast Cancer Trialists’ Collaborative Group, 1998.297
Most trials used a tamoxifen dose of 20mg/day. There is no evidence that higher doses offer better outcomes.294
In trials of one or two years duration of tamoxifen, there is a trend towards greater improvement in recurrence-free survival among older women, but this trend is weaker in the more recent trials involving about 5 years of adjuvant tamoxifen, where the analyses are limited to patients with positive or unknown ER.297
There is strong evidence that adjuvant tamoxifen therapy reduces the incidence of contralateral breast cancer (Level I).45,297The protective effect is more marked with longer periods of adjuvant therapy, and 5 years of tamoxifen approximately halves this risk. This protective effect on contralateral breast cancer is similar in women whose first breast cancer was ER-positive or ER-negative.297
Tamoxifen’s weak oestrogenic action also induces an increase in bone mineral density and altered blood lipid patterns. While these changes might lead to a reduction in cardiovascular events and deaths, no such reduction could be demonstrated (or refuted) in the most recent overview data.297
The Oxford overview concluded that currently available trial results still leave substantial uncertainty as to whether tamoxifen should continue to be routinely taken beyond 5 years.297