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Purpose: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS., Patients and Methods: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972)., Results: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS., Conclusions: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race., (©2024 American Association for Cancer Research.)

Recent clinical trials have demonstrated activity of chemoimmunotherapy with interleukin-2 (IL-2), interferon-[alpha], and 5-fluorouracil (5-FU) in advanced renal cell cancer. A phase II study was performed to evaluate the affect of adding the potentiating agent leucovorin to this combination regimen. Treatment courses consisted of IL-2 5 MIU/m2 subcutaneously days 1, 3, and 5 of weeks 1 to 4, interferon-[alpha] 3 MIU/m2 subcutaneously on days 1, 3, and 5 of weeks 1 to 4, and leucovorin 50 mg/m2 IV followed by 5-FU 450 mg/m2 IV infusion weekly weeks 1 to 4. Patients were given no treatment on weeks 5 and 6 of the 6-week treatment cycle. Of the 20 patients enrolled in the study, 16 were evaluable for toxicity and 15 were evaluable for tumor response. The most severe toxicities included three reports of grade IV diarrhea; overall, nine incidents of grade III or IV toxicity were reported. No objective antitumor responses were observed, and the median time to progression was 2.8 months. We conclude that this combination chemoimmunotherapy regimen has substantial toxicity but no significant antitumor activity in patients with advanced stage renal cell carcinoma.

The toxicity and marginal effectiveness of cytotoxic chemotherapy in metastatic non-small cell lung cancer (NSCLC) necessitates the search for new agents. Preliminary data in lung cancer and other malignant and premalignant disorders have identified retinoid compounds as potentially useful antitumor agents. Twenty-eight patients with metastatic NSCLC were treated with oral all-trans retinoic acid in a phase II trial. The study population consisted of patients with excellent performance status and minimal weight loss. Toxicities were generally mild and included cutaneous effects, headache, and myalgia. A significant number of patients developed elevations of hepatic transaminases or hyperlipidemia and 3 patients had treatment-related leukocytosis. Two patients (8%) achieved a partial response, and 1 had a mixed response. The duration of remission in the 2 responders was 7 and 13 months and the median survival of all patients 7 months. Therefore, all-trans retinoic acid has minimal activity as a single agent in NSCLC but warrants further study in combination with biological agents and chemotherapy.

Current therapies for the treatment of malignancies are associated with significant toxicity, as chemotherapy and radiation therapy do not discriminate between normal and malignant cells. One approach to ameliorating the toxicity associated with therapy is through the use of chemoprotective agents. This article reviews a variety of agents that have been evaluated as possible protectants, including WR-2721 and the colony-stimulating factors. It is hoped that the understanding of how to optimally use chemoprotective agents will lead to more tolerable treatments for patients, and possibly allow for dose-escalation, which may contribute to improvement in patient survival.

A case of phenytoin-carbamazepine cross-sensitivity is presented. Similar signs and symptoms occurred during administration of both drugs. A common metabolic intermediate is offered as a possible explanation of the mechanism. Clinicians should be careful when choosing alternatives in patients with hypersensitivity reactions to anticonvulsants. Valproic acid may be the safest choice in this setting.