Jack L. Watkins

Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer.

Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta‐adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]).

Fatal Diffuse Alveolar Damage Associated with Oxaliplatin Administration

Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer in both the adjuvant and metastatic disease settings. Significant improvements in survival have resulted from the use of oxaliplatin-based combinations. This article describes the use of oxaliplatin-based chemotherapy in a patient with stage III colon cancer who developed fatal diffuse alveolar damage during his adjuvant therapy. Other cases of pulmonary toxicity associated with oxaliplatin use are presented and the proposed pathophysiology of this rare occurrence is discussed.

Chemotherapy for gynecologic cancers.

This review highlights significant recent developments and trends in chemotherapy for major gynecologic malignancies, i.e., ovarian cancer, endometrial cancer, uterine sarcomas, gestational trophoblastic neoplasia, and cervical cancer. In ovarian cancer, chemotherapeutic options for early, advanced and recurrent disease are in the adjuvant setting as well as in the neoadjuvant setting are explored. For uterine cancer, adjuvant chemotherapy is employed for high risk epithelial subtypes with early disease, such as uterine papillary serous carcinomas, uterine carcinosarcomas and leiomyosarcomas, advanced stage cases, as well as recurrent disease. The review then proceeds to further discuss the appropriate treatment based on the International Federation of Gynecology and Obstetrics prognostic scoring system for gestational trophoblastic neoplasia. Finally, chemotherapy is utilized in cervical cancer as neo-adjuvant therapy prior to surgery or radiation, as a sensitizer concomitantly with radiation therapy or for the treatment of advanced and recurrent disease.

Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide (VPCBAE) in the management of three patients with small-cell carcinoma of the ovary.

► Ovarian small-cell carcinoma of the hypercalcemic type is a rare neoplasm with no standard treatment. ► The chemotherapy regimen including vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin and etoposide (VPCBAE) has limited toxicities and was effective in the 3 patients described in this case report.

Rhabdomyolysis in a Prostate Cancer Patient Taking Ketoconazole and Simvastatin: Case Report and Review of the Literature

OBJECTIVE To report a case of severe rhabdomyolysis resulting in acute renal failure caused by an interaction between ketoconazole and simvastatin in a patient with prostate cancer. CASE SUMMARY A 64-year-old man who received ketoconazole for prostate cancer, along with simvastatin and fenofibrate for dyslipidemia, presented to our ambulatory clinic with complaints of blood in his urine and weakness following an increase in his ketoconazole dose. Two days after presentation, the patient was admitted with rhabdomyolysis and acute renal failure, as evidenced by elevated serum creatine kinase (>32,000 IU/L), serum myoglobin (20.6 ng/mL), and serum creatinine (4.2 mg/dL) as well as abnormal bone scintigraphy findings. Ketoconazole, fenofibrate, and simvastatin were discontinued. Renal function did not normalize with hydration, and intermittent hemodialysis was initiated; 10 days of hemodialysis resulted in normalization of electrolytes and creatine kinase. Symptom improvement and normalization of laboratory parameters were observed after prolonged hospitalization (24 days). DISCUSSION Prostate cancer is the most common malignancy among men in the US. Androgen deprivation therapy is the standard initial treatment for biochemical recurrence or metastatic disease. Most patients experience progression to a castrate-resistant disease state, requiring the use of additional therapies. Ketoconazole is considered a secondary hormonal treatment option. We describe an interaction in a patient with prostate cancer between a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and ketoconazole resulting in rhabdomyolysis, requiring hemodialysis. An objective causality assessment using the Horn Drug Interaction Probability Scale revealed that the adverse drug reaction was a possible result of the interaction. CONCLUSIONS The temporal fashion in which the episode occurred suggests that a possible simvastatin-ketoconazole interaction precipitated rhabdomyolysis in this patient. The use of ketoconazole for castrate-resistant prostate cancer can lead to drug-drug interactions in patients taking simvastatin or other HMG-CoA reductase inhibitors. Clinicians should be aware of this severe adverse event and take steps to minimize its occurrence.

Evaluation of pegylated liposomal doxorubicin dose on the adverse drug event profile and outcomes in treatment of recurrent endometrial cancer

Objective This study aims to determine factors that may increase the likelihood of adverse drug events (ADEs) in patients with recurrent endometrial cancer treated with pegylated liposomal doxorubicin (PLD) as well as this agent’s impact on clinical outcomes. Methods The treatment records of patients with endometrial cancer who received PLD at The University of Texas, MD Anderson Cancer Center, from 1996 to 2006 were reviewed. Patient demographics, PLD dose, ADEs, use of supportive care interventions, disease progression, and survival were extracted. Logistical regression analysis was used to identify factors that were associated with higher incidence of ADEs and that influenced survival. Results A total of 60 patients with recurrent endometrial cancer were identified who experienced 122 ADEs. The most commonly reported ADEs were nausea (18.9%), palmar-plantar erythrodysesthesia (PPE; 16.4%), muscle weakness (12.3%), mucositis (10.7%), and peripheral neuropathy (9.8%). Seventeen patients (28%) required a dose reduction because of ADEs. However, only 5 (8.3%) patients discontinued therapy because of toxicity. Cooling mechanisms were used in 19 patients to prevent PPE, although 9 of these patients still experienced PPE. Treatment with 6 or more cycles of PLD was associated with increased incidence of neutropenia (P = 0.045), peripheral neuropathy (P = 0.004), and PPE (P < 0.001). No differences in progression-free survival or time to progression were found between the doses of PLD; however, there was an assessable trend toward increased survival with doses of 40 mg/m2. Conclusions Although there was no association with dose level and ADEs, more cycles received increased the incidence of toxicities, including PPE and neuropathy. There was no association between different doses of PLD and progression-free survival or time to progression.

Case Report - Aripiprazole-Induced Diabetic Ketoacidosis: Remaining Vigilant

Purpose A case of hyperglycemia and subsequent diabetic ketoacidosis (DKA) possibly associated with aripiprazole use in an adult patient with no previous history of diabetes mellitus is reported. Summary A 55-year-old man presented to the emergency department with altered mental status and complaints of nausea, vomiting, and abdominal pain. The patients past medical history was significant only for depression and hyperlipidemia. His home medications included sertraline 200 mg once daily and aripiprazole 10 mg once daily, which was initiated 6 months prior. The patient had no documented history of diabetes mellitus. Laboratory test results at the time of admission revealed hyponatremia, elevated serum creatinine, a blood glucose of 714 mg/dL, elevated amylase and lipase, and ketonuria. The patients hemoglobin A1C was 13.5%. DKA was diagnosed. The patient was admitted to the hospital and given a normal saline bolus and infusion. Home medications were not continued. An insulin infusion was also initiated. On the second day of admission, his blood glucose continued to decrease, the insulin infusion was slowly titrated down, and NPH was started. On hospital day 3, the NPH was increased and the insulin infusion was discontinued. The patient was discharged home following 4 days of hospitalization on insulin therapy and aripiprazole was not restarted. Conclusions Although the glucose dysregulatory effect of aripiprazole is not widely appreciated, our case report emphasizes the importance of monitoring patients who receive any atypical antipsychotic, particularly aripiprazole, for glucose and metabolic abnormalities.

Extensive cutaneous metastases of ovarian cancer after prolonged response to liposomal doxorubicin

Highlights • Cutaneous metastases are rare and clinically challenging to manage. When present, they often represent end-stage disease.• Treatments for cutaneous metastases are limited, and primarily palliative in nature.

Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer: Beta-Blockers and Ovarian Cancer Survival

Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta‐adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]).

Clinical Impact of Selective and Non-selective Beta Blockers on Survival in Ovarian Cancer Patients

Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta‐adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]).