Time to Update Evidence-Based Guideline Recommendations About Concurrent Tamoxifen and Antidepressant Use? A Systematic Review.

Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with concurrent use. It remains unclear however whether this interaction is clinically important. A systematic review of studies comparing endocrine therapy (including tamoxifen and aromatase inhibitors) alone or concurrent with antidepressants in breast cancer patients was performed. The literature search sought studies within MEDLINE, EMBASE, and the Cochrane Collaboration Library published from database inception until December 1, 2020. Outcomes of interest included recurrence, breast cancer-specific survival, overall mortality, quality of life, and treatment compliance. Studies were assessed with the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle Ottawa tool for case-control and cohort studies. From 695 citations, we included 15 studies (2 randomized controlled trials [255 patients], 10 retrospective cohort studies [75,678 patients], and 3 case-control studies [18,836 patients]). While between-study clinical and methodologic differences (including analysis of confounding variables) precluded formal meta-analysis, findings from included studies did not find consistent evidence that concurrent use of antidepressants (including paroxetine) with tamoxifen therapy has negative impacts on the outcomes of interest. In this systematic review, despite data from nearly 100,000 patients, concurrent use of tamoxifen and antidepressants showed no consistent negative effect on clinical outcomes. Given the recognized harm to patients of changing either endocrine therapy or antidepressants to avoid concurrent use, current evidence-based guidelines should be updated accordingly. More rigorously designed pharmacoepidemiologic studies are needed.

Feasibility of using a pragmatic trials model to compare two primary febrile neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC).

PURPOSE: Optimal primary febrile neutropenia (FN) prophylaxis (i.e. ciprofloxacin or granulocyte-colony stimulating factors [G-CSF]) for patients receiving docetaxel-cyclophosphamide (TC) chemotherapy is unknown. We assessed the feasibility of using a novel pragmatic comparative effectiveness trial to compare these standard-of-care options. METHODS: Early-stage breast cancer patients receiving TC chemotherapy were randomised to either ciprofloxacin or G-CSF. Trial methodology consists of broad eligibility criteria, simply-defined endpoints, integrated consent model incorporating oral consent, and web-based randomisation in the clinic. Primary feasibility endpoints included patient and physician engagement (if > 50% of patients approached agree to participate and if > 50% of physicians approached patients for the study). Secondary clinical endpoints included the following: first occurrence rates of FN, treatment-related hospitalisation, or chemotherapy dose reduction/delay/discontinuation, as well as patient satisfaction with the oral consent process. RESULTS: Of 204 patients approached, 91.2% (186/204) agreed to randomisation. Sixteen of twenty (80%) participating medical oncologists randomised patients. Median patient age was 57.7 (range 31.8-84.1). The 186 patients received 557 cycles of chemotherapy. Overall incidences of first events by patient (n = 186) were as follows: FN (18/186, 21.43%), treatment-related hospitalisation (11/186, 13.10%), chemotherapy reduction (19/186, 22.62%), chemotherapy discontinuation (16/186, 19.05%), and chemotherapy delays (5/186, 5.95%). A total of 37.77% (69/186) of patients and 12.39% (69/557) of chemotherapy cycles had at least one of these first events. Patients were highly satisfied with the oral consent process. CONCLUSION: This study met its feasibility endpoints. This model offers a means of comparing standard-of-care treatments in a practical and cost-efficient manner. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov : NCT02173262.

Taxane acute pain syndrome (TAPS) in patients receiving taxane-based chemotherapy for breast cancer-a systematic review.

BACKGROUND: Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 24-48 h after taxane-based chemotherapy and lasting for 5-7 days. Relatively little is known about its incidence and impact on quality of life. OBJECTIVES: A systematic review was conducted evaluating the incidence of TAPS in breast cancer patients receiving taxane-based chemotherapy. METHODS: Embase, Cochrane, and Ovid MEDLINE were searched from 1947 to July 2015. Data was sought from randomized controlled trials (RCTs), prospective and retrospective observational studies. Two reviewers independently screened citations and full text articles. Outcomes of interest were the incidence of TAPS and its impact on quality of life. RESULTS: Of 980 citations identified, 51 relevant studies (27,007 patients) were included. Data came from RCTs (12,357 patients), retrospective (6566 patients) and prospective observational studies (6210 patients). Study sample sizes ranged from 14 to 4149 patients (median 152). Given the significance between study heterogeneity, a meta-analysis was not performed. The incidence of TAPS varied between taxanes: paclitaxel (median 13.1 %, range 0.9-86 %), docetaxel (median 10.5 %, range 3.6-70 %), and nab-paclitaxel (26 %, range 14-43 %). In the metastatic setting, median incidence was 30 % (range 5.4-73 %), compared with 11.3 % (range 0.9-86 %) in the adjuvant setting. Three out of eight studies assessing quality of life demonstrated pain interference with daily activities. CONCLUSIONS: The incidence of TAPS varies between taxanes, regimens, and disease settings. In order to identify patients at the greatest risk of TAPS, and hence optimize its prevention and management, standardized methods of diagnosing and measuring TAPS are needed.

Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy-a systematic review.

BACKGROUND: Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 1-3 days and lasting 5-7 days after taxane-based chemotherapy. Despite negatively impacting patient's quality of life, little is known about the optimal TAPS management. A systematic review of treatment strategies for TAPS across all tumor sites was performed. METHODS: Embase, Ovid MEDLINE(R), and the Cochrane Central Register of Controlled Trials were searched from 1946 to October 2014 for trials reporting the effectiveness of different treatments of TAPS in cancer patients receiving taxane-based chemotherapy. Two individuals independently screened citations and full-text articles for eligibility. Outcome measures included type of treatment and response of myalgias, arthralgias, pain, and quality of life (QoL). RESULTS: Of 1614 unique citations initially identified, five studies met the pre-specified eligibility criteria. Two were randomized placebo-controlled trials (225 patients), two were randomized open-label trials 76 patients), and one was a retrospective study (10 patients). The agents investigated included gabapentin, amifostine, glutathione, and glutamine. Study sizes ranged from 10 to 185 patients. Given the heterogeneity of study designs, a narrative synthesis of results was performed. Neither glutathione (QoL, p = 0.30, no 95 % CI reported) nor glutamine (mean improvement in average pain was 0.8 in both treatment arms, p = 0.84, no 95 % CI reported) were superior to placebo. Response to amifostine (pain response) and gabapentin (reduction in taxane-induced arthralgias and myalgias) was 36 % (95 % CI, 16-61 %) and 90 % (no 95 % CI data reported), respectively. CONCLUSIONS: Despite its prevalence in patients receiving taxane-based chemotherapies, TAPS remains poorly researched and few studies evaluate its optimal management. If the management of patients is to be improved, more prospective trials are needed.