Incidence, risk factors, and management of infusion-related reactions in breast cancer patients receiving trastuzumab.

BACKGROUND: Trastuzumab has become a mainstay of therapy for human epidermal growth factor receptor-2 overexpressed breast cancer in nearly all stages of the disease. Like many monoclonal antibodies, trastuzumab is associated with infusion-related reactions (IRRs) that are not well described, and incidence varies widely between reports (0.7%-40% of patients). MATERIALS AND METHODS: A retrospective chart review of breast cancer patients who received trastuzumab was conducted. The primary objective was to describe the incidence, risk factors, and management of IRRs during the first 12 weeks of trastuzumab therapy in a general population of breast cancer patients. RESULTS: A total of 197 patients who received trastuzumab (1,788 doses) were evaluated. Thirty-three IRRs were identified in 32 patients, resulting in an incidence of 16.2% of patients and 1.8% of doses. All IRRs were mild or moderate in severity and were successfully managed with supportive medications and/or by temporarily stopping the infusion. All patients received subsequent cycles of trastuzumab, with only one patient experiencing a subsequent reaction. Body mass index, stage of disease, and use of premedications were significantly associated with IRRs by multivariate logistic regression analysis. CONCLUSION: Overall, these results support that the vast majority of IRRs occur with the first infusion, are mild in severity, and are easily managed. In addition, risk factors were identified that may help to identify a population of patients at increased risk of IRRs who may benefit from premedication.

Pilot study to assess toxicity and pharmacokinetics of docetaxel in patients with metastatic breast cancer and impaired liver function secondary to hepatic metastases.

BACKGROUND: Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction. METHODS: Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patient's level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression. RESULTS: Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy. CONCLUSIONS: Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.

Pertuzumab: a new targeted therapy for HER2-positive metastatic breast cancer.

Trastuzumab, a humanized monoclonal antibody, has become an important targeted therapy for patients with all stages of human epidermal growth factor receptor-2 (HER2)-positive breast cancer. However, primary and acquired resistance to trastuzumab remains a significant problem. Pertuzumab, a humanized monoclonal antibody that binds to a domain of the HER2 receptor separate from trastuzumab, may have the potential to overcome trastuzumab resistance. Clinical trials have shown that pertuzumab can be effectively combined with other biologic therapy or chemotherapy in patients with metastatic HER2-positive breast cancer. Pertuzumab is relatively well tolerated with minimal increases in hematologic and cardiac toxicity observed when added to trastuzumab and/or docetaxel. In addition to becoming the standard of care in combination with docetaxel and trastuzumab in patients with newly diagnosed HER2-positive metastatic breast cancer, clinical trials continue to evaluate pertuzumab in combination with other targeted therapy, chemotherapy, and in patients with early stage breast cancer. These trials will help to further determine the role of pertuzumab in the treatment of HER2-positive breast cancer.

Chemotherapy outcomes for the treatment of unresectable intrahepatic and hilar cholangiocarcinoma: a retrospective analysis.

BACKGROUND: Recent clinical trials for "biliary cancers" include a heterogenous group of patients with cholangiocarcinoma, gallbladder, and ampullary cancers. Limited data exist regarding the relative effectiveness of known chemotherapeutic regimens specifically in intrahepatic or hilar cholangiocarcinoma. METHODS: Records of M D Anderson Cancer Center patients with unresectable intrahepatic and hilar cholangiocarcinoma who received first-line chemotherapy from January 1, 2005, to October 31, 2009, were retrospectively reviewed. The primary objective of this research was to determine overall tumor control rates with chemotherapeutic regimens used for first-line treatment of unresectable intrahepatic and hilar cholangiocarcinoma. Secondary objectives included duration of response, overall survival, and prognostic factors. RESULTS: Eighty-five patients met inclusion criteria and were eligible for analysis. The most commonly used regimen was gemcitabine/cisplatin (62%), followed by oxaliplatin and capecitabine (16%). There was no significant difference between tumor control rates with gemcitabine/cisplatin (72% PR + SD) and other regimens (69% PR + SD). There was no significant difference between overall survival with the use of gemcitabine/cisplatin (15.2 months) or alternative regimens (13.9 months). A decrease in overall survival was seen with elevated baseline CA 19-9 (p < .0001), an initial diagnosis of unknown primary tumor (p = .0001), and prior treatment with chemoradiation (p = .0018). CONCLUSION: In this retrospective review, both gemcitabine/cisplatin and alternative doublets (including capecitabine/oxaliplatin, gemcitabine/capecitabine, and gemcitabine/oxaliplatin) were effective regimens in maintaining disease control in intrahepatic and hilar cholangiocarcinoma.

Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome.

OBJECTIVE: To evaluate evidence for use of aromatase inhibitors for ovulation induction and pregnancy in patients with polycystic ovary syndrome (PCOS). DATA SOURCES: A MEDLINE search (1966-May 2009) was conducted using the search terms anastrozole, aromatase inhibitors, exemestane, letrozole, ovulation, and polycystic ovary syndrome to identify relevant studies. STUDY SELECTION AND DATA EXTRACTION: Prospective clinical trials published in English and conducted in humans were identified. Trials using intrauterine insemination methods for pregnancy were excluded. The resulting articles were separated into 2 groups: aromatase inhibitor use in clomiphene-resistant patients and use in treatment-naïve patients. Eleven trials were reviewed. DATA SYNTHESIS: Accepted pharmacologic treatments for women with PCOS and infertility include clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone (GnRH) analogs. Each medication has variable efficacy rates and adverse effects. Therefore, other treatments are needed for a subset of women with PCOS and infertility. Evidence suggests that nonsteroidal aromatase inhibitors, specifically letrozole and anastrozole, may have ovulation-inducing effects by inhibiting androgen-to-estrogen conversion. Select trials with aromatase inhibitors have demonstrated efficacy for increased endometrium thickness, ovulation rates, and pregnancy rates when used in clomiphene citrate-resistant or treatment-naïve patients. CONCLUSIONS: Further trials comparing aromatase inhibitors with clomiphene citrate are necessary before aromatase inhibitors can be recommended routinely for ovulation induction in women with PCOS and infertility. However, aromatase inhibitors may be considered in a subset of this population, specifically women who are clomiphene citrate resistant or those who, after discussion of risks and benefits, are not candidates for clomiphene citrate, gonadotropins, or GnRH analogs.