Updating clinical recommendations for breast, colorectal and lung cancer treatments: an opportunity to improve methodology and clinical relevance.

BACKGROUND: clinical guidelines can improve quality of care summarising available knowledge and proposing recommendations for health care decisions. Being up to date is one of their quality requisites. Little experience is available on when and how guidelines should be updated. We report on the update process of evidence-based clinical recommendations on anticancer drugs. METHODS: three multidisciplinary panels, supported by methodology experts, updated the recommendations. The methodologists were in charge of the qualitative and quantitative synthesis of the evidence. The panels were responsible for the final decision about risk/benefit profile of the drugs and strength of the recommendations. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used. RESULTS: six recommendations out of 15 were completely updated in 8 months time. In four cases, the strength of the recommendation changed; in two of them, we moved from a weak to a strong positive one. Despite the increased certainty about the positive risk/benefit profile, this was translated in a change in the strength of the recommendation only in one case out of three. Three recommendations were refined making them more clinically specific. CONCLUSIONS: accumulation of evidence is an opportunity for guideline panels to refine methodological rigour, clinical relevance and to foster consensus on recommendations. This requires time and resource investments.

Managing severe cancer pain: the role of transdermal buprenorphine: a systematic review.

Pain is a frequent and important symptom in cancer patients. Among the available strong opioids, transdermal buprenorphine has been licensed in Europe since 2002, and results from a few clinical studies suggest that it may be a good alternative to the other oral or transdermal opioids. To assess the best available evidence on its efficacy and safety, we carried out a systematic literature review with the aim of pooling relevant studies. We identified 19 eligible papers describing 12 clinical studies (6 randomized controlled trials and 6 observational prospective studies), including a total of about 5000 cancer patients. Given the poor quality of reports and the heterogeneity of methods and outcomes, pooling was not feasible as the type of data was not appropriate for combining the results statistically. A meta-analysis based on individual data is ongoing in the context of the Cochrane Collaboration. In conclusion, although the narrative appraisal of each study suggests a positive risk benefit profile, well designed and statistically powered controlled clinical trials are needed to confirm this preliminary evidence.

Follow-up strategies for women treated for early breast cancer.

BACKGROUND: Follow-up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. OBJECTIVES: To assess the effectiveness of different policies of follow-up for distant metastases on mortality, morbidity and quality of life in women treated for stage I, II or III breast cancer. SEARCH STRATEGY: We searched, the Breast Cancer Group's specialized register (May 14, 2004), the Cochrane Controlled Trial Register (Cochrane Library Issue 1, 2004), Medline (January 1966 - May 2004) and EMBASE (1988 - May 2004). References from retrieved articles were also checked. SELECTION CRITERIA: All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow-up after primary treatment were reviewed for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and eligibility for inclusion in the review. Data were pooled in an individual patient data meta-analysis for the two RCTs testing the effectiveness of different follow-up schemes. Subgroup analyses were conducted by age, tumour size and lymph node status. MAIN RESULTS: Four RCTs involving 3055 women with breast cancer (clinical stage I, II or III) were included. Two of these involving 2563 women compared follow-up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio 0.96, 95% confidence interval 0.80 to 1.15) or disease-free survival (hazard ratio 0.84, 95% confidence interval 0.71 to 1.00) emerged. No differences in overall survival and disease-free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. In 1999, 10-year follow-up data became available for Rosselli Del Turco and no significant differences in overall survival were found. One RCT (296 women) compared follow-up performed by a hospital-based specialist to follow-up performed by general practitioners. No significant differences in time to detection of recurrence and quality of life emerged. Patient satisfaction was greater among patients treated by general practitioners. One RCT (196 women) compared regularly scheduled follow-up visits to less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of GP's consultations. AUTHORS' CONCLUSIONS: This updated review of RCTs conducted almost 20 years ago suggest that follow-up programs based on regular physical examinations and yearly mammography alone are as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life. In one RCT, follow-up care performed by trained general practitioners working in an organized practice setting had comparable effectiveness to that delivered by hospital-based specialists in terms of quality of life and time to detection of distant metastases.

Determination of platinum in plasma of patients affected by inoperable lung carcinoma treated with radiotherapy and concurrent low-dose continuous infusion of cis-dichlorodiammine platinum(II).

Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion of cis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m2 daily for 100 h/week for 5 weeks, and the infusions were separated by 68 h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5-day continuous infusions at much higher daily doses. Nevertheless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule.