NCHA variable combination as a method to undertake LGBTQ + student subpopulation analyses.

ObjectiveCombine National Collegiate Health Assessment (NCHA) measures indicating LGBTQ + membership into a single variable in order to analyze health responses of this group as compared to their cisgender, heterosexual (cis-het) peers. Participants: Students at a liberal arts university who completed the Spring 2019 NCHA-II study (n = 1107). Methods: Four different NCHA sexual orientation and gender identification variables were combined, creating a new variable to examine the campus LGBTQ + student sub-sample as a single, complete group. That group was then compared to cis-het students across multiple variables. Results: LGBTQ + students reported statistically significant differences for key variables such as suicide attempts, suicidal ideation, and self-harm, as well as for stressors that impact academic success such as discrimination. Conclusions: This analysis indicates that the challenges campus LGBTQ + students face are much different than their cis-het peers. Support from campus community members is suggested to reduce negative impacts for these students.

Prospective evaluation of drug-drug interactions in ambulatory cancer patients initiated on prophylactic anticoagulation.

INTRODUCTION: Drug options for VTE prophylaxis are increasing for ambulatory cancer patients and data regarding anticoagulant-drug interactions and their relationship to VTE and bleeding are needed to improve care. METHODS: Over one year, 108 cancer patients with high VTE risk were prospectively identified. Potential anticoagulant-drug interactions were ascertained by chart review and graded on need for intervention. Providers selected anticoagulant prophylaxis based on potential drug interactions and patient-provider discussion. A cross-sectional analysis was performed thereafter to evaluate VTE and bleeding endpoints within one year of anticoagulant initiation. RESULTS: The average number of potential drug interactions per patient was higher for warfarin than others (3.04 vs. 1.28 (apixaban), 1.02 (rivaroxaban), and 0.98 (LMWH)). The severity of the interactions based on grade was, for apixaban: 1.6% grade X, 50.8% grade D, and 47.5% grade C; for rivaroxaban: 2.1% grade X, 64.9% grade D, 33.0% grade C; for LMWH, 0% grade X, 66.7% grade D, 33.3% grade C; and for warfarin, 0% grade X, 29.4% grade D, 70.6% grade C. At the end of the investigational period, 11 bleeds and 7 VTEs were reported. Drug combinations significantly associated with an increased bleeding risk were crizotinib with apixaban or rivaroxaban and PPIs with warfarin. The use of sulfamethoxazole-trimethoprim with warfarin was associated with an increased VTE risk. CONCLUSIONS: DOACs had fewer DDIs than warfarin, although interaction severity differed between anticoagulants. Some anticoagulant-drug interactions were associated with bleeding or VTE. Although not powered for analysis, DDI severity did not affect bleeding rates and inversely correlated with VTE risk.

An Anaphylactoid Reaction to Rattlesnake Envenomation in a Pediatric Patient.

Rattlesnake envenomation causes a spectrum of symptoms and signs, many of which closely resemble an anaphylactic reaction. Development of airway compromise after a snake bite to an extremity is unusual, but has been previously reported. The majority of such reports detail a history of probable sensitization from previous contact with snakes or snake venom. Few reports exist without such previous contact; no reports are of pediatric cases. Here we present a 14-year-old boy with no history of prior snake exposure who presents with an anaphylactoid reaction after a rattlesnake bite.

Dexamethasone premedication for prophylaxis of taxane toxicities: can the doses be reduced when paclitaxel or docetaxel are given weekly?

PURPOSE: To evaluate the clinical literature supporting reduced doses of dexamethasone to prevent taxane hypersensitivity reactions (HSRs), and edema/skin toxicities in respect to docetaxel, when taxanes are given weekly, as opposed to every 3 weeks. DATA SOURCE: Clinical literature of human-controlled clinical trials, accessed through MEDLINE and meeting abstract databases (from 1990 to 2010). DATA EXTRACTION: The retrieved literature was reviewed to include all human clinical trials that recorded adverse effect information with weekly taxanes utilizing reduced-dose or tapering dexamethasone schemas, either prospectively or retrospectively. DATA SYNTHESIS: Prophylaxis for paclitaxel-related HSRs generally includes one or more 20 mg doses of dexamethasone, with histamine-1 and -2 receptor antagonists prior to infusion of paclitaxel. Prophylaxis for docetaxel-related HSRs generally includes dexamethasone beginning 1 day before docetaxel, and continuing twice daily for a total of 3 days. These schedules were designed for taxanes given every 3 weeks, but may lead to steroid-related adverse effects when given weekly with weekly taxane administration. Treatment strategies designed to reduce corticosteroid exposure in patients receiving weekly taxanes have been investigated. CONCLUSIONS: Several predication strategies utilizing reduced doses of dexamethasone with weekly taxanes appear to be feasible and safe, and can be considered for patients experiencing, or at high risk for steroid-induced side effects. However, the optimal schedule is not yet determined; larger prospective clinical trials are needed.

Current combination chemotherapy regimens for metastatic breast cancer.

PURPOSE: To review the role of combination therapy in the treatment of metastatic breast cancer and to describe strategies to help manage adverse events associated with combination therapy. SUMMARY: Although the median survival of patients with metastatic breast cancer has increased over the last several decades, new treatment options are needed to further improve survival and quality of life for these patients. Novel cytotoxic and noncytotoxic agents have recently been evaluated in combination regimens for patients with metastatic breast cancer. Combinations for metastatic breast cancer that appear in recently approved labeling include ixabepilone with capecitabine, and the targeted biological agent lapatinib in combination with capecitabine. Ixabepilone is the first of a new family of cytotoxic agents--the epothilones--to enter clinical practice. Similar to the taxanes, ixabepilone binds to and stabilizes intracellular microtubules, resulting in decreased DNA replication and cell proliferation. Ixabepilone possesses antitumor activity in taxane-resistant tumor cells and has been shown to significantly improve progression-free survival when used in combination with capecitabine in patients with taxane-resistant tumors. Lapatinib, an oral small-molecule inhibitor of human epidermal growth factor receptors-1 and -2, has been shown, when combined with capecitabine, to improve progression-free survival in patients with advanced metastatic breast cancer who had progressed on prior therapy. The combination of paclitaxel and bevacizumab carries approved labeling for treatment of metastatic breast cancer, although there are concerns about bevacizumab and the risk of toxicity. CONCLUSION: Ongoing clinical trials continue to define the role of novel antitumor agents in combination regimens for patients with metastatic breast cancer. Targeted agents are less likely to produce adverse events that are typical of cytotoxic chemotherapy but, because of their effects on specific molecular targets, may cause toxicities that were previously uncommon in cancer therapy.

Is there a taxane-free interval that predicts response to taxanes as a later-line treatment of recurrent ovarian or primary peritoneal cancer?

OBJECTIVES: Taxanes have reported response rates of 20% to 40% in recurrent ovarian cancer (ROC) but are less well studied as a later-line treatment. We reviewed our experience with taxanes in ROC to determine (1) if a taxane-free interval is associated with response rates in women with ROC and (2) if the use of intervening therapy (IT) affects subsequent response rates to taxanes. METHODS: We retrospectively identified women who received first- or second-line platinum-taxane therapy and later received a single-agent taxane. Demographics, intervening regimens, and follow-up and survival data were collected. Responses were characterized by cancer antigen 125 levels based on the Gynecologic Cancer InterGroup serologic response definitions. RESULTS: We identified 46 women who met the eligibility criteria. The median age was 57 years (range, 39-78 years). The median interval between taxanes was 25.8 months (range, 2.9-85.5 months), with 10 (21%) of the women were treated 12 months or less from their last taxane and 37 (79%) treated more than 12 months. The median number of IT was 2 (range, 0-5). Forty patients (87%) received paclitaxel; 6 (13%) received docetaxel. All patients treated 12 months or less from their last taxane responded (P = 0.02). The number of IT was associated with a better response; all women (100%) treated who had no IT, 7 (54%) of 13 women with 1 to 2 ITs, and 7 (39%) of 18 women with 3 ITs or more responded. The overall survival was 13.4 months in responders versus 10.6 months in nonresponders (P = 0.27). CONCLUSIONS: Taxanes maintain an activity as a later-line agent, even with 3 or more intervening therapies. However, the highest responses were seen if taxanes were used within 12 months of the last platinum-based combination. The lack of an increased response with aprolonged taxane-free interval is likely related to the number of IT, consistent with the emergence of multidrug resistance.

Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.

OBJECTIVES: Although many clinicians practice empiric dose reduction to prevent toxicity, it is unknown whether obese patients given chemotherapy dosed according to actual body weight (ABW) experience excess toxicity. At our institution, cancer patients receive chemotherapy dosed by ABW unless on a protocol capping doses at a maximum body surface area (BSA). We compared toxicities and dose modifications between women with a BSA>2 m(2) on uncapped versus capped paclitaxel as part of adjuvant paclitaxel/carboplatin for gynecologic malignancy. METHODS: In this retrospective study, women with a BSA>2 m(2) treated with paclitaxel (P) and carboplatin (C) for endometrial and ovarian cancer between January 1999 and July 2007 were identified using the chemotherapy database. Records were reviewed for patient age, BSA, diagnosis, stage, standardized and actual doses for each cycle, adverse drug reactions, and dosing modifications. Statistical comparisons were made using Fisher's exact test. RESULTS: We identified 59 women with BSA>2 m(2) on adjuvant P/C for endometrial and ovarian cancers. 50 received paclitaxel dosed by ABW and 9 received paclitaxel capped at a BSA of 2 m(2). There were no statistically significant differences in rates of toxicity or dose modification. CONCLUSIONS: Obese women with a BSA>2 m(2) on paclitaxel dosed by ABW do not experience excess toxicity in comparison to women on paclitaxel capped at a maximum BSA or women in published trials of adjuvant P/C. Empiric dose reduction is unnecessary and may result in suboptimal treatment of obese patients. However, as this was a retrospective review, more research is needed to make definitive recommendations on this topic.

Effects of chemotherapy during pregnancy on the placenta.

Whereas the effects of chemotherapy during pregnancy for mother and fetus are well described, its effects on the placenta remain largely undetermined. We performed a retrospective clinicopathologic analysis of the placenta following chemotherapy. Charts were reviewed for type of malignancy, type and timing of chemotherapy, and fetal and pregnancy outcome. Placentas were studied by standard pathologic analysis as well as computer-assisted morphometry and fluorescence in situ hybridization (FISH) analysis. Patients (n = 13) underwent chemotherapy during pregnancy for carcinoma of breast (3), ovary (2), cervix (2), salivary gland (1), lymphoma/leukemia (4), or rhabdomyosarcoma (1). Eleven patients were treated with DNA-active cytotoxic agents during the 2nd and/or 3rd trimesters; their placentas showed nonspecific findings, including villous hypermaturity, distal villous hypoplasia, villous edema, and excessive extravillous trophoblast, and 4/11 (36%) were small-for-age. In one case (rhabdomyosarcoma), the mother was exposed to cytotoxic agents throughout the entire pregnancy. In this case, associated with severe congenital anomalies, the placenta showed striking nuclear pleomorphism of the extravillous trophoblast of the chorion laeve, associated with FISH-demonstrated hyperpolyploidy. One patient was treated with the targeted tyrosine kinase inhibitor, imatinib, in 2 consecutive pregnancies; these placentas showed no specific anomalies. Our findings suggest that chemotherapy during the 1st trimester induces excessive polyploidization of the chorion laeve trophoblast, likely representing an adaptive response to intraamniotic toxins. Second and 3rd trimester exposure to cytotoxic agents may predispose to placental underdevelopment. However, without appropriate controls (untreated patients with equivalent malignancies), the specific effects of chemotherapy in this group are difficult to assess.

Regional chemotherapy: a focus on hepatic artery infusion for colorectal cancer liver metastases.

Regional infusion strategies have been used as a treatment modality in multiple cancers, including ovarian, appendiceal, and colorectal cancers. Perhaps the most illustrative use of regional therapy is that of hepatic arterial infusion (HAI) for liver metastases from colorectal cancer. The administration of chemotherapy by HAI is logical and has theoretic advantages over systemic chemotherapy for the treatment of hepatic metastases from colorectal cancer. With the use of an appropriately chosen chemotherapy agent, HAI can generate an increase in hepatic tumor drug exposure as compared with intravenous delivery of the same agent. This article reviews the pharmacologic benefits of HAI therapy and the contemporary trials performed and underway.

Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from Women and Infants' Hospital.

OBJECTIVES: Carboplatin (C) is a standard treatment for gynecologic cancers, but its use in recurrence is associated with an increased risk of hypersensitivity reactions (HSR) in those previously treated with C. However, there is no way to predict those at risk for a C-HSR. We sought to evaluate whether the platinum-free interval (PFI) was predictive of incidence and severity of HSRs. METHODS: Patients treated with C between 1/99 and 12/2005 were identified through our chemotherapy database. Records were reviewed in those receiving multiple C regimens or with C HSR. Severity was defined as mild or severe based on symptoms. RESULTS: 126 patients were identified who had multiple C regimens. 63 (50%) experienced C HSRs of which 36 (29%) were severe. The incidence of C HSR was 25.8% for PFI < 12 months and 56.5% if > or = 12 months (p=0.0023). The incidence of a severe C HSR significantly increased with time as well: 6.5% PFI < 12 months, 23.9% PFI 12-24 months and 47% PFI > or = 24 months (p=0.0091). Of those receiving a 3rd regimen of C, 8/8 had a HSR and these were severe in seven (88%). Of note, 60 patients received > 8 (range 9-19) cycles with the first C regimen, and none of the patients reacted after cycle 8. CONCLUSIONS: A duration of greater than 12 months between C regimens is associated with an increased risk of both any--and severe--HSR. Our data also suggests that upfront treatment with C beyond eight cycles is not associated with an increased risk of HSR.

Elevated body mass index does not increase the risk of palmar-plantar erythrodysesthesia in patients receiving pegylated liposomal doxorubicin.

OBJECTIVES: The dose-limiting toxicity of pegylated liposomal doxorubicin (PLD) is palmar-plantar erythrodysesthesia (PPE). Some physicians are reluctant to use this drug in overweight patients, postulating that larger size increases the likelihood of PPE. We sought to determine whether a correlation exists between body mass index (BMI) and the frequency or severity of skin reactions during PLD chemotherapy. METHODS: The records of all patients receiving PLD chemotherapy for gynecologic malignancy at our institution were reviewed for chemotherapy history, BMI at start of treatment, dose, infusion time, and adverse outcomes. Skin reaction sites, grade, and treatments were recorded. Possible predisposing factors were extracted, as well as the reason for drug discontinuation. RESULTS: Over 7 years, 103 patients were treated with PLD for gynecologic malignancies. 429 cycles were given, and PPE occurred in 36% of patients treated. Of those with PPE, reactions were grades 1, 2, or 3 in 54%, 32%, and 14% of patients, respectively. The BMI of patients with PPE (29.0) was not significantly different from that of patients without PPE (28.8). Analysis using finer subsets of weight also revealed no association. Finally, logistic regression revealed no relationship between BMI and rash grade. CONCLUSIONS: Elevated BMI does not appear to correlate with occurrence of PPE in our population. Of interest, among patients discontinuing PLD due to skin toxicity, 25% had clinical evidence of response. The identification of predisposing risk factors may help guide treatment decisions; however, elevated BMI does not appear to be such a risk factor.

Cross-sensitivity between paclitaxel and docetaxel in a women's cancers program.

PURPOSE: With the use of steroid premedication, the incidence of severe hypersensitivity reactions (S-HSR) to paclitaxel is estimated to be 2%. For those who develop a S-HSR to paclitaxel, docetaxel has been employed as an alternative agent though the presence of cross-sensitivity has not been established. We sought to define the incidence of S-HSR to docetaxel following a paclitaxel S-HSR in an academic women's cancer program. METHODS: Patients treated with either paclitaxel (P) or docetaxel (D) between 11/1999 and 8/2004 were identified through our pharmacy database. Records were reviewed and data collected on those patients who had a S-HSR, defined as symptoms for which drug was discontinued, to P, D, or both. RESULTS: 718 patients received P and 93 received D. 59 received D following treatment with P. The presence of S-HSR for P was 2.2% (16/718 patients) and for D was 9.7% (9/93 patients). 10 patients with S-HSR to P crossed over to D and all nine patients reacting to D had a prior reaction to T for a cross-sensitivity rate of 90% (9/10 patients). CONCLUSIONS: Cross-sensitivity of D after P was 90% at our institution. Given the different vehicles used in P and D, it is likely attributed to the taxane moiety. Caution is required with re-challenge of patients with docetaxel if they have previously reacted to paclitaxel.

Two for good measure: six versus eight cycles of carboplatin and paclitaxel as adjuvant treatment for epithelial ovarian cancer.

INTRODUCTION: Although the standard of care for advanced epithelial ovarian cancer (EOC) is six cycles (6C) of platinum-taxane (PT), there have been no studies on the optimal duration of treatment in the era of adjuvant taxanes. At our center, some women receive eight cycles (8C) of PT, based on physician judgment. We were interested in evaluating the outcomes of women treated with 8C of PT for EOC as compared to a cohort who received 6C. METHODS: We retrospectively identified women with Stage III or IV EOC between 1998 and 2003 who received 6C or 8C of PT. The endpoints were disease-free (DFS) and overall survival (OS). CA-125 response was defined as a decrease in CA-125 of 50% in four serial samples or of 75% over three samples. RESULTS: One hundred and twenty-two women met criteria for inclusion; 84 received 6C, and 38 received 8C. Comparing the cohorts receiving 6C versus 8C, 71% versus 26% were optimally debulked (P < 0.01). 79 patients were evaluable by CA-125 (52 6C/27 8C), and all responded. 88% receiving 6C and 81% receiving 8C normalized their CA-125 at end of treatment (P = 0.20). The proportion with a normal CA-125 at Cycle 2 was 29% versus 12%, respectively (P = 0.15) and, at Cycle 4, was 88% versus 36%, respectively (P < 0.01). DFS was 13 months with 6C and 8 months with 8C (P = 0.01). OS was 31 versus 23.5 months (P = 0.02), respectively. When the survival analysis is restricted to suboptimal debulked patients only, the DFS is 12.5 versus 8 months (P = 0.02), and OS is 32 versus 26.5 months (P = 0.15), respectively. CONCLUSIONS: Two further cycles of PT did not improve DFS or OS for patients with advanced EOC. Patients who do not achieve remission after 6C are unlikely to benefit from additional chemotherapy using the same agents and should be considered for clinical trials involving novel agents with different mechanisms of action.