Gershon Y. Locker

ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer

PURPOSEnTo update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of gastrointestinal cancers.nnnMETHODSnFor the 2006 update, an update committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of Medline and the Cochrane Collaboration Library were performed. The Update Committees literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies.nnnRECOMMENDATIONS AND CONCLUSIONnFor colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) be ordered preoperatively, if it would assist in staging and surgical planning. Postoperative CEA levels should be performed every 3 months for stage II and III disease for at least 3 years if the patient is a potential candidate for surgery or chemotherapy of metastatic disease. CEA is the marker of choice for monitoring the response of metastatic disease to systemic therapy. Data are insufficient to recommend the routine use of p53, ras, thymidine synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, microsatellite instability, 18q loss of heterozygosity, or deleted in colon cancer (DCC) protein in the management of patients with colorectal cancer. For pancreatic cancer, CA 19-9 can be measured every 1 to 3 months for patients with locally advanced or metastatic disease receiving active therapy. Elevations in serial CA 19-9 determinations suggest progressive disease but confirmation with other studies should be sought. New markers and new evidence to support the use of the currently reviewed markers will be evaluated in future updates of these guidelines.

2000 Update of Recommendations for the Use of Tumor Markers in Breast and Colorectal Cancer: Clinical Practice Guidelines of the American Society of Clinical Oncology*

OBJECTIVEnTo update the 1997 clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials.nnnOPTIONSnSix tumor markers for colorectal cancer and eight for breast cancer were considered. They could be recommended or not for routine use or for special circumstances. In addition to carcinoembryonic antigen (CEA) and CA 15-3, CA 27.29 was also considered among the serum tumor markers for breast cancer.nnnOUTCOMESnIn general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used.nnnEVIDENCEnA computerized literature search from 1994 to March 1999 was performed.nnnVALUESnThe same values for use, utility, and levels of evidence were used by the committee.nnnBENEFITS, HARMS, AND COSTSnThe same benefit, harms, and costs were used.nnnRECOMMENDATIONnChanges were recommended (see Appendix).nnnVALIDATIONnThe updated recommendations were validated by external review by the American Society of Clinical Oncologys (ASCOs) Health Services Research Committee and by ASCOs Board of Directors.nnnSPONSORnAmerican Society of Clinical Oncology.

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial

BACKGROUNDnThe Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to assess the safety, tolerability, and risk-benefit indices of these compounds.nnnMETHODSnWe analysed postmenopausal women (mean age 64 years [SD 9]) with localised breast cancer randomly assigned to anastrozole (n=3125) or tamoxifen (n=3116). Efficacy measures, including death and risk-benefit indices, were analysed by intention to treat. Safety analyses were based on treatment first received (n=3092 for anastrozole and n=3094 tamoxifen). We calculated a risk-benefit analysis using the two global indices for the Womens Health Initiative and for Disease-Free Survival and Serious Adverse Events. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.nnnFINDINGSnAt median follow-up of 68 months (range 1-93), treatment-related adverse events occurred significantly less often with anastrozole than with tamoxifen (1884 [61%] vs 2117 [68%]; p<0.0001), as did treatment-related serious adverse events (146 [5%] vs 277 [9%]; p<0.0001) and adverse events leading to withdrawal (344 [11%] vs 442 [14%]; p=0.0002). Patients given anastrozole had significantly fewer overall events for the Global Index of the Womens Health Initiative (744 [24%] vs 851 [27%]; hazard ratio 0.85 [95% CI 0.77-0.94], p=0.001) and the Global Index of Disease-Free Survival and Serious Adverse Events (1453 [46%] vs 1594 [51%]; 0.88 [0.82-0.94]; p=0.0004).nnnINTERPRETATIONnAnastrozole is tolerated better than tamoxifen by postmenopausal women with early-stage breast cancer, and results in fewer serious adverse events. Furthermore, it has a more favourable overall risk-benefit profile and lower recurrence rate than tamoxifen.

Quality of Life of Postmenopausal Women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial

PURPOSEnTo determine the quality of life (QoL) of women participating in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial during the first 2 years of treatment.nnnPATIENTS AND METHODSnA total of 1,021 women were enrolled onto the QoL subprotocol. All had completed primary treatment (surgery +/- radiotherapy +/- chemotherapy) and were to receive 5 years of adjuvant treatment with anastrozole (n = 335), tamoxifen (n = 347), or a combination (n = 339) of both. Patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) plus endocrine subscale (ES) at baseline and 3, 6, 12, 18, and 24 months, or until disease recurrence. The primary end point was the FACT-B Trial Outcome Index (TOI). The secondary end point was the ES total score. Analyses of individual endocrine symptoms were also explored.nnnRESULTSnQuestionnaire completion approximated 85% of assessments available for analysis. Overall QoL for all groups improved from baseline during the 2-year period. There were no significant differences in TOI or ES scores across treatment groups. Endocrine symptoms increased between baseline and 3 months for all groups and stabilized thereafter. There were some small differences in side effect profiles. Compared with patients receiving tamoxifen only, patients receiving anastrozole only reported significantly fewer cold sweats and vaginal discharge, yet more vaginal dryness, painful intercourse, and loss of sexual interest.nnnCONCLUSIONnTwo years of treatment with anastrozole, tamoxifen, or the combination had a similar overall QoL impact, showing gradual improvement over time. Endocrine-related symptoms for all three arms worsened initially and recovered partially during 2 years. The different symptoms experienced may assist in decision making about treatment and supportive care needs.

Quality of Life of Postmenopausal Women in the ATAC ("Arimidex", Tamoxifen, Alone or in Combination) Trial after Completion of 5 years' Adjuvant Treatment for Early Breast Cancer

The impact of treatment on health-related quality of life (HRQoL) is an important consideration in the adjuvant treatment of operable breast cancer. Here we report mature HRQoL outcomes from the ATAC trial, comparing anastrozole with tamoxifen as primary adjuvant therapy for postmenopausal women with localized breast cancer. Patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire plus endocrine subscale (ES) at baseline, 3 and 6xa0months, and every 6xa0months thereafter. Baseline characteristics in the HRQoL sub-protocol were well balanced between the anastrozole (nxa0=xa0335) and tamoxifen (nxa0=xa0347) groups in the primary analysis population. As with previously published results at 2xa0years, there was no statistically significant difference in the Trial Outcome Index of the FACT-B, the primary endpoint of the study, between treatments at 5xa0years. There were no statistically significant differences between treatment groups in ES total scores. Consistent with the 2-year analysis, there were differences between treatment groups in patient-reported side effects: diarrhea (anastrozole 3.1% vs. tamoxifen 1.3%), vaginal dryness (18.5% vs. 9.1%), diminished libido (34.0% vs. 26.1%), and dyspareunia (17.3% vs. 8.1%) were significantly more frequent with anastrozole compared to tamoxifen. Dizziness (3.1% vs. 5.4%) and vaginal discharge (1.2% vs. 5.2%) were significantly less frequent with anastrozole compared to tamoxifen. In this, the first report of HRQoL over 5xa0years of initial adjuvant therapy with an aromatase inhibitor, we conclude that anastrozole and tamoxifen had similar impacts on HRQoL, which was maintained or slightly improved during the treatment period for both groups.

The spectrum of vascular lesions in the mammary skin, including angiosarcoma, after breast conservation treatment for breast cancer

BACKGROUNDnWith the general acceptance of lumpectomy, axillary staging, and radiotherapy as local treatment for infiltrating breast cancer, an appreciation is evolving for the spectrum of vascular lesions that occur in the mammary skin after this treatment. Most of these lesions develop within the prior radiation field after breast conservation treatment.nnnSTUDY DESIGNnA retrospective chart and slide review was conducted, consisting of five patients with cutaneous vascular lesions after breast conservation treatment for infiltrating breast cancer.nnnRESULTSnThe latent time interval from definitive treatment of breast cancer to the clinical recognition of vascular lesions ranged from 5 to 11 years. Two patients did not have either arm or breast edema, two patients had breast edema, and the fifth patient had arm edema. Lesions arising in the irradiated mammary skin included extensive lymphangiectasia (one), atypical vascular lesions (two), and cutaneous angiosarcoma (four).nnnCONCLUSIONSnAtypical vascular lesions at the skin margins of mastectomy may be predictive of recurrence after resection of angiosarcoma. Excision of skin from the entire radiation field may be necessary to secure local control of the chest wall in patients with cutaneous angiosarcoma after therapeutic breast radiotherapy.

Cost-effectiveness analysis of anastrozole versus tamoxifen as primary adjuvant therapy for postmenopausal women with early breast cancer: a US healthcare system perspective. The 5-year completed treatment analysis of the ATAC ('Arimidex', Tamoxifen Alone or in Combination) trial.

BackgroundThis study evaluated the cost-effectiveness of anastrozole versus generic tamoxifen for primary adjuvant treatment of postmenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC), from a US healthcare perspective.MethodsA probabilistic Markov model was developed using the 5-year completed treatment analysis of the ATAC (‘Arimidex’, Tamoxifen Alone or in Combination) trial (ISRCTN 18233230) to project outcomes for anastrozole and tamoxifen to 25xa0years. Resource utilization data were obtained primarily from published literature and a physician survey (including expert opinion from ATAC Steering Committee members). Drug costs were taken from published wholesale acquisition costs (anastrozole

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium.

6.56/day, generic tamoxifen

Cost-effectiveness analysis of anastrozole vs tamoxifen in adjuvant therapy for early stage breast cancer in the United Kingdom: the 5-year completed treatment analysis of the ATAC ('Arimidex', Tamoxifen alone or in combination) trial.

1.33/day). Other unit costs (

Bevacizumab (B) plus gemcitabine (G) in patient (pts) with advanced pancreatic cancer (PC): Updated results of a multi-center phase II trial

US 2003–4) were from standard sources. Utility estimates of relevant health states, used to compute quality-adjusted life-years (QALYs), were collected using the standard gamble technique in a cross-sectional sample of 44 patients. Costs and benefits were discounted 3% annually.ResultsIn a cohort of 1000 postmenopausal women with HR+ EBC, the model showed anastrozole treatment (versus tamoxifen) would lead to 257xa0QALYs gained (0.26 QALYs gained per patient), at an additional cost of