Alopecia With Endocrine Therapies in Patients With Cancer

Background.

Whereas the frequency of alopecia to cytotoxic chemotherapies has been well described, the incidence of alopecia during endocrine therapies (i.e., anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents are widely used in the treatment and prevention of many solid tumors, principally those of the breast and prostate. Adherence to these therapies is suboptimal, in part because of toxicities. We performed a systematic analysis of the literature to ascertain the incidence and risk for alopecia in patients receiving endocrine therapies.

Methods.

An independent search of citations was conducted using the PubMed database for all literature as of February 2013. Phase II–III studies using the terms “tamoxifen,” “toremifene,” “raloxifene,” “anastrozole,” “letrozole,” “exemestane,” “fulvestrant,” “leuprolide,” “flutamide,” “bicalutamide,” “nilutamide,” “fluoxymesterone,” “estradiol,” “octreotide,” “megestrol,” “medroxyprogesterone acetate,” “enzalutamide,” and “abiraterone” were searched.

Results.

Data from 19,430 patients in 35 clinical trials were available for analysis. Of these, 13,415 patients had received endocrine treatments and 6,015 patients served as controls. The incidence of all-grade alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence interval: 3.3%–5.9%). The highest incidence of all-grade alopecia was observed in patients treated with tamoxifen in a phase II trial (25.4%); similarly, the overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen (6.4%). The overall relative risk of alopecia in comparison with placebo was 12.88 (p < .001), with selective estrogen receptor modulators having the highest risk.

Conclusion.

Alopecia is a common yet underreported adverse event of endocrine-based cancer therapies. Their long-term use heightens the importance of this condition on patients'' quality of life. These findings are critical for pretherapy counseling, the identification of risk factors, and the development of interventions that could enhance adherence and mitigate this psychosocially difficult event.     

A Patient With Medullary Thyroid Carcinoma Associated With Polyneuropathy

A 41-year-old female with sporadic medullary thyroid carcinoma(MTC) had a sensorimotor polyneuropathy manifested by progressivenumbness and muscle weakness in all of her extremities. Therewas marked improvement in the neurological disorder followingremoval of the MTC. Her endocrine and neurological findingsand the possible relationship between MTC and polyneuropathyare discussed.     

Less Satisfaction With Information in Patients With Prostate Cancer Treated With Surgery and Salvage Radiotherapy Compared With Patients Treated With Curative Radiotherapy Alone,Despite Similar Health-Related Quality of Life

BackgroundThis study examined patient perception of information received, satisfaction with that information, and its relation to health-related quality of life (HRQoL) and clinical and demographic variables before, during, and after radiotherapy (RT) for localized prostate cancer.Patients and MethodsIn 2010, 2 questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and EORTC QLQ information module [QLQ-INFO25]) were sent to 660 consecutive patients with prostate cancer who had undergone or were to undergo RT with curative intent between December 2006 and March 2010.ResultsThe response rate was 92%. Although most patients (69%) were satisfied with the information they received, statistically significant differences were found for all but 2 EORTC QLQ-INFO25 variables, favoring those who were treated with RT alone compared with those treated with both prostatectomy and salvage RT. Statistically significant associations between all HRQoL variables and satisfaction with information were found; higher levels of satisfaction were associated with better functioning and lower levels of symptoms and problems.ConclusionSatisfaction with the information received was studied in patients with prostate cancer with localized disease. Despite the fact that the majority of patients reported being satisfied with the information received, there is room for improvement, especially regarding “the disease,” “other services,” “different places of care,” and “things you can do to help yourself.” Patients treated with both prostatectomy and salvage RT reported significantly lower levels of satisfaction with information received and of having received significantly less information than did patients treated with RT alone.     

Prognostic Factors Associated With Disease Progression and Overall Survival in Patients With Myelodysplastic Syndromes Treated With Decitabine

BackgroundMyelodysplastic syndromes (MDS) progress to acute myeloid leukemia (AML) in approximately 30% of patients. Identification of risk factors for progression to AML and overall survival (OS) would help guide treatment decisions.Patients and MethodsWe investigated prognostic factors for progression to AML and survival in 163 patients with MDS treated with decitabine 15 mg/m² over 3 hours every 8 hours for 3 days every 6 weeks (n = 74) or 20 mg/m² over 1 hour daily for 5 days every 4 weeks (n = 89).ResultsMultivariate analysis of pooled baseline data revealed that only study effect was associated with progression to AML. A hemoglobin value at least 10 g/dL, platelet count at least 50 × 10³/μL, and lack of chromosome 5 or 7 abnormalities were associated with longer OS.ConclusionsPatients with certain prognostic factors should be considered for other interventions in addition to decitabine treatment.     

Patients With Lung Cancer With Metachronous or Synchronous Gastric Cancer

BackgroundThere are few reports of treatment and outcome for patients with metachronous or synchronous lung and gastric cancers. To evaluate them, we conducted a retrospective study.Patients and MethodsThe medical records of patients with lung cancer who previously or simultaneously had gastric cancer seen in our division between January 1979 and July 2008 were reviewed.ResultsForty-five (3.2%) of 1391 patients had previous or simultaneous gastric cancer. The proportion of men was higher among patients with lung cancer with gastric cancer than those without (P = .0006). There was a significant difference in age at the time of diagnosis of lung cancer between the 45 patients with gastric cancer and the 1346 patients without it (P = .0344). The proportion of smokers was higher among lung cancer patients with gastric cancer than those without (P = .0015). Twenty-seven of 45 patients had smoking-related cell types of lung cancer: squamous cell carcinoma and small-cell lung cancer. The proportion of these 2 cell types was higher in patients with lung cancer with gastric cancer than those without (P = .02). The diagnosis of gastric cancer preceded the diagnosis of lung cancer in 33 patients, and the median duration from the diagnosis of gastric cancer to that of the lung cancer was 6 years.ConclusionFor patients with gastric cancer, smoking cessation, a chest radiograph at least yearly for several years, and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended, especially in elderly men with gastric cancer and smoking habit.     

Predicting Thrombocytopenia in Patients With Breast Cancer Treated With Ado-trastuzumab Emtansine

IntroductionThrombocytopenia is a common and potentially serious adverse event of ado-trastuzumab emtansine (T-DM1) use in patients with advanced breast cancer. However, the risk factors have been minimally explored. Our aim was to develop a clinical prediction model from the clinicopathologic data that would allow for quantification of the personalized risks of thrombocytopenia from T-DM1 usage.Materials and MethodsData from 3 clinical trials, EMILIA (a study of trastuzumab emtansine versus capecitabine + lapatinib in participants with HER2 [human epidermal growth factor receptor 2]-positive locally advanced or metastatic breast cancer), TH3RESA (a study of trastuzumab emtansine in comparison with treatment of physician's choice in participants with HER2-positive breast cancer who have received at least two prior regimens of HER2-directed therapy), and MARIANNE [a study of trastuzumab emtansine (T-DM1) plus pertuzumab/pertuzumab placebo versus trastuzumab (Herceptin) plus a taxane in participants with metastatic breast cancer], were pooled. Cox proportional hazard analysis was used to assess the association between the pretreatment clinicopathologic data and grade ≥ 3 thrombocytopenia occurring within the first 365 days of T-DM1 use. A multivariable clinical prediction model was developed using a backward elimination process.ResultsOf the 1620 participants, 141 (9%) had experienced grade ≥ 3 thrombocytopenia. On univariable analysis, the body mass index, race, presence of brain metastasis, platelet count, white blood cell count, and concomitant corticosteroid use were significantly associated with the occurrence of grade ≥ 3 thrombocytopenia (P < .05). The multivariable prediction model was optimally defined by race (Asian vs. non-Asian) and platelet count (100-220 vs. 220-300 vs. >300 × 10⁹/L). A large discrimination between the prognostic subgroups was observed. The highest risk subgroup (Asian and platelet count of 100-220 cells ×10⁹/L) had a 40% probability of grade ≥ 3 thrombocytopenia within the first 365 days of T-DM1 therapy compared with 2% for the lowest risk subgroup (non-Asian and platelet count > 300 × 10⁹/L).ConclusionA clinical prediction model, defined by race and pretreatment platelet count, was able to discriminate subgroups with a significantly different risk of grade ≥ 3 thrombocytopenia after T-DM1 initiation. The model allows for improved interpretation of the personalized risks and risk/benefit ratio of T-DM1.     

Temozolomide With or Without Radiotherapy in Melanoma With Unresectable Brain Metastases

Summary Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m² temozolomide on days 1 to 5 every 28 days as first or second-line therapy. This therapy regimen was combined with radiotherapy of the brain metastases in 22/35 patients. Grade III and IV toxicity was observed in 8/35 patients (leukopenia, granulocytopenia, thrombocytopenia, anemia, nausea and obstipation). Complete remission was observed in 1/34, partial remission in 2/34 and stable disease in 9/34 patients. In 5/34 a mixed response was assessed, 17/34 had disease progression and in one patient tumor response was not evaluable. The median progression free time was 5 (0–8) months for all patients, the median survival time for all patients from start of therapy was 8 (0–28) months, 9 (2–28) months in patients with concurrent stereotactic radiotherapy and 7 (3–17) months in patients with concurrent whole brain radiotherapy. Our results demonstrate that temozolomide can be combined with radiotherapy for the treatment of brain metastases in malignant melanoma, and that this combination may prolong survival in this patient group.     

Outcomes in Organ Transplant Recipients With Prostate Cancer Treated With Radiotherapy

Background

Few data exist in the literature regarding outcomes of men with prostate cancer (CaP) who are receiving immunosuppression from prior organ transplantation. The aim of this study was to evaluate biochemical disease-free survival, distant metastasis–free survival, overall survival, and toxicity in patients with organ transplants who were later treated with definitive radiotherapy for CaP.

Features Associated With Long-Term Survival in Patients With Metastatic Breast Cancer

BackgroundOf women diagnosed with metastatic breast cancer (MBC), 20% to 30% survive ≥5 years. We evaluated data from a large breast cancer program to identify features associated with MBC survival.Patients and MethodsWomen diagnosed with MBC in or after 1999 were included. Long-term MBC survival was defined as ≥5 years from date of MBC diagnosis (n = 122), short-term MBC survival as ≤2 years (n = 191). Differences were assessed using t tests, Wilcoxon–Mann–Whitney tests, χ², and Fisher exact tests. Odds ratios (ORs) were calculated using multivariate logistic regression models.ResultsLong-term survivors were significantly (P < .05) younger, premenopausal, partnered, had estrogen receptor (ER)-positive, progesterone receptor-positive, and HER2-positive disease, lower Charlson Comorbidity Index, lower rates of visceral metastases, and higher household income. After adjustment for potential confounders, de novo MBC, premenopausal status, ER-positive status, and HER2-positive status remained significantly positively associated with long-term survival (respectively: OR, 2.68 [95% confidence interval (CI), 1.48-4.88]; OR, 1.96 [95% CI, 1.02-3.79]; OR, 3.74 [95% CI, 1.72-8.14]; OR, 2.88 [95% CI, 1.61-5.14]). Triple-negative status, visceral with bone metastases, and brain metastases remained negatively associated with long-term survival (respectively: OR, 0.12 [95% CI, 0.05-0.29]; OR, 0.18 [95% CI, 0.07-0.47]; OR, 0.16 [95% CI, 0.04-0.60]). Partner status and household income were significant in univariate but not multivariate analyses.ConclusionDiagnosis of de novo MBC, premenopausal status, ER-positive status, and HER2-positive status were positively associated whereas triple-negative status, brain metastases, and visceral with bone metastases were inversely associated with long-term survival. These findings can be applied to better prognosticate survival for MBC patients.     

Clinical Experience With Ibrutinib Alone or in Combination With Either Cytarabine or Azacitidine in Patients With Acute Myeloid Leukemia

BackgroundPreclinical studies have suggested a role for Bruton tyrosine kinase (BTK) as a potential therapeutic target in acute myeloid leukemia (AML), and anti-AML activity in vivo has been demonstrated with BTK inhibitors.Patients and MethodsIn this open-label phase 2a study, patients with AML were treated with ibrutinib 560 mg per day alone (cohort 1; n = 7), or ibrutinib in combination with either cytarabine 20 mg administered subcutaneously twice daily for 10 days of a 28-day cycle (cohort 2; n = 21) or azacitidine 75 mg/m² administered intravenously once daily on days 1 to 7 of a 28-day cycle (cohort 3; n = 8). Best overall response (primary end point), overall survival, and safety were summarized.ResultsA total of 36 patients were enrolled and received treatment; median duration of ibrutinib treatment was 5.4 weeks, and median time on study was 16 months. Of 24 patients evaluable for response, 1 partial remission (cohort 3) and 1 complete remission (cohort 2) were observed; the remaining responses were treatment failures. Median overall survival was 4.0 months in cohort 1, 2.2 months in cohort 2, 2.8 months in cohort 3, and 2.4 months for the overall population. No unexpected safety signals were identified. Grade 3 or higher adverse events that occurred in ≥ 10% of patients included AML progression, febrile neutropenia, pneumonia, anemia, thrombocytopenia, fatigue, asthenia, and respiratory failure.ConclusionIbrutinib alone or in combination with cytarabine or azacitidine demonstrated an acceptable safety profile. However, limited efficacy with ibrutinib was observed in patients with AML.     

Infectious Complications Among Patients With AML Treated With Immune Checkpoint Inhibitors

BackgroundThe incidence and spectrum of infections in acute myeloid leukemia (AML) patients treated with immune checkpoint inhibitors (CPIs) in combination with a hypomethylating agents (HMAs) is not known. Nivolumab is a PD-1 checkpoint inhibitor approved in many solid tumors and lymphoma.Materials/MethodsWe performed a retrospective cohort study of 75 adult patients at MD Anderson Cancer Center with relapsed/refractory AML treated with azacitidine and nivolumab or with nivolumab and ipilimumab from March 2016 through March 2020 and described the infectious complications that occurred during their treatment.ResultsSixty-four (85%) patients developed an infection during the study period, and bacterial infections were by far the most common type of infection. A comparison of risk factors and characteristic between the 75 patients on CPIs who developed infection and those who did not found that corticosteroid use (odds ratio [OR], 28; 95% confidence interval [CI], 1.6-490; P =.02) and lymphopenia (OR, 4; 95% CI, 1-15.5; P =.04) were significantly associated with infections.ConclusionPatient with relapsed/refractory AML treated with salvage CPI-based therapy were more likely to develop infections when treated with corticosteroids in the setting of an immune-related adverse event, compared to those who were not.     

Cabozantinib Safety With Different Anticoagulants in Patients With Renal Cell Carcinoma

BackgroundIn patients with renal cell carcinoma (RCC) on cabozantinib, venous thromboembolism (VTE) management remains challenging due to limited safety data regarding direct oral anticoagulants (DOACs) use in conjunction with cabozantinib. We investigated the safety of cabozantinib with different anticoagulants in patients with RCC.MethodsIn this retrospective multicenter study (9 sites), patients with advanced RCC were allocated into 4 groups: (1) cabozantinib without anticoagulation, cabozantinib with concomitant use of (2) DOACs, (3) low molecular weight heparin (LMWH), or (4) warfarin. The primary safety endpoint was the proportion of major bleeding events (defined per International Society on Thrombosis and Hemostasis criteria). The primary efficacy endpoint was the proportion of new/recurrent VTE while anticoagulated.ResultsBetween 2016 and 2020, 298 patients with RCC received cabozantinib (no anticoagulant = 178, LMWH = 41, DOAC = 64, and warfarin = 15). Most patients had clear cell histology (78.5%) and IMDC intermediate/poor disease (78.2%). Cabozantinib was first, second, or ≥ third line in 21.8%, 31.9%, 43.3% of patients, respectively. Overall, there was no difference in major bleeding events between the no anticoagulant, LMWH, and DOAC groups (P = .088). Rate of new/recurrent VTE was similar among anticoagulant groups. Patients with a VTE had a statistically significantly worse survival than without a VTE (HR 1.48 [CI 95% 1.05-2.08, P = .02]).ConclusionThis real-world cohort provides first data on bleeding and thrombosis complications in patients with RCC treated with cabozantinib with or without concurrent anticoagulation. DOACs appear safe for VTE treatment for patients with RCC on cabozantinib, but optimized anticoagulation management, including individualized risk-benefit discussion, remains important in clinical practice.     

Feasibility of Therapy With Hypomethylating Agents in Patients With Renal Insufficiency

BackgroundTo our knowledge, the feasibility of therapy with hypomethylating agents (HAs) in patients with renal insufficiency (RI) has not been examined.Patients and MethodsWe reviewed 41 patients with a diagnosis of acute myeloid leukemia (n = 17), myelodysplastic syndromes (n = 15), and chronic myelomonocytic leukemia (n = 9) who had RI and were receiving therapy with azacitidine or decitabine. The median number of administered cycles was 3. Most patients (39; 95%) received a standard dose of the drugs at the initiation of therapy. Nine patients (22%) required treatment interruptions or discontinuation, and 10 patients (24%) required dose reductions.Results:The overall response rate was 63%, and 4 patients (10%) achieved a complete response. Twenty patients (51%) experienced grade 3 or 4 myelosuppression-related toxicities. Hospitalization was required in 68% of the patients. Among 12 patients with an estimated glomerular filtration rate of 29 mL per minute or less, 6 required dose reductions attributable to myelosuppression (n = 3) or to worsening renal function (n = 3). The overall survival (OS) at 18 months was 12%, and the median OS was 8.6 months.ConclusionThe use of HA in patients with RI is feasible, but is associated with a higher incidence of toxicity. Dose adjustments and the use of growth factor may be necessary for some patients.