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ABSTRACT: The purpose of this review article is to present the current treatment options for castrate resistant prostate cancer in addition to the recently approved agents and their role in treatment.
The biology of prostate cancer and the data supporting the use of traditional chemotherapeutic options in castrate resistant prostate cancer are reviewed. The newly approved agents, sipuleucel-T, cabazitaxel, and abiraterone, are presented as well. The studies that led to the approval of these three agents are discussed in this article as well as their current and potential roles in the treatment of castrate resistant prostate cancer.
New mechanisms, drugs, and clinically relevant molecular targets show survival advantage and are new options available for patients after traditional chemotherapy. The roles of these new agents have yet to be further clarified in future studies.
Journal of Oncology Pharmacy Practice 02/2012; 18(3):343-54.
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ABSTRACT: Treating two active malignancies concurrently can be exceedingly difficult. Complications can occur from the different treatment regimens, especially if they share common targets, and the progressing diseases can make managing treatment side-effects even more challenging. We report a case of a patient with coexisting CML and mRCC who progressed on multiple lines of mRCC therapy while experiencing significant dose limiting side-effects.
Journal of Oncology Pharmacy Practice 12/2011; 17(4):436-9.
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ABSTRACT: Pneumatosis intestinalis (PI) occurs when inter-luminal air enters the bowel wall of the gastrointestinal tract via a mucosal defect. The condition is caused by numerous disease states, direct trauma, and various drugs. When PI is secondary to drug therapy, discontinuation of the offending agent results in the resolution of PI. We report on the case of a 73-year-old male with a history of refractory gastrointestinal stromal tumor experiencing PI while on sunitinib treatment. PI was noted via computed tomography (CT) scans 68 days after starting sunitinib therapy and showed near complete resolution on a follow up CT performed one month after discontinuing sunitinib. Given that a CT scan performed five months prior to the initiation of sunitinib did not show PI, lack of abdominal symptoms in our patient, and resolution of PI after discontinuing sunitinib, the cause of PI in our patient was likely due to sunitinib treatment.
Anticancer research 10/2011; 31(10):3429-32. · 1.73 Impact Factor
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ABSTRACT: Current vancomycin dosing guidelines in our acute myeloid leukemia population too often achieve suboptimal initial drug concentrations. Our aim was to assess vancomycin pharmacokinetic parameters in acute myeloid leukemia patients and develop an improved dosing equation to attain more accurate initial therapeutic trough levels. Acute myeloid leukemia patients receiving vancomycin for a presumed or documented gram positive infection were eligible. Patients hospitalized in the intensive care unit, those with creatinine clearance <30 mL/min or with limb amputation were excluded. Three samples were collected at the following post-infusion time ranges: 1 h, 3-8 h, and 8-24 h post-infusion, contingent on the dosing interval. Pharmacokinetic data were then fit using a Bayesian-based population pharmacokinetic model. A total of 25 acute myeloid leukemia patients were studied with a mean volume in the central compartment (Vc; L/65 kg), volume of distribution at steady state (Vss; L/65 kg) and distributional clearance (CLd; L/h/65 kg) of 15, 38.9, and 9.32, respectively. CLslope was 0.59 (mg of vancomycin clearance per unit of creatinine clearance in mL/min); this value is 21.4% lower than the established literature value (0.75). The derived equation, based upon these values, was reasonably precise at achieving the desired trough concentration using a priori dosing. The mean (CV%) of the achieved trough was 94% (29%) with a range of 66-188%; 3/25 at <75% and >125%]. We have established that the derived dosing equation can place ≈ 75% of adult acute myeloid leukemia patients at vancomycin trough levels within 75-125% of the target trough level.
Journal of Oncology Pharmacy Practice 04/2011; 18(1):91-6.
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ABSTRACT: Cancer therapeutics is undergoing a revolution with the advent of new drugs that can selectively target molecules responsible for carcinogenesis and tumor growth. The type and mechanism of these targeting drugs vary. Some are small molecules that specifically target a binding site on a receptor or signal transduction molecule. Antibodies have been engineered to bind to the receptors or the corresponding ligands that mediate a critical cancer activity. In almost all cases, the intent is to inhibit or shut down a specific molecular pathway. Unprecedented activity against the cancer is seen without overt traditional toxicities such as alopecia, nausea and/or vomiting, and cytopenias. Unfortunately, an increase in toxicity has now become evident as more experience accumulates with the use of these drugs. In some cases, unexpected cardiotoxicities have arisen when these new drugs have been added to more conventional chemotherapies. Heart failure is the unfortunate manifestation for many of these toxicities. We outline the scope of this problem and examine the mechanisms of drug-induced heart failure. The distinctive signs and symptoms specific to each drug are described, and the diagnosis and treatment of the condition are discussed. Our aim is to allow the practitioner to recognize the unusual manifestations of heart failure in this setting in order to make a timely diagnosis and begin appropriate treatment measures.
Pharmacotherapy 01/2011; 31(1):62-75. · 2.90 Impact Factor
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ABSTRACT: Colistin is a polymyxin antibiotic that was discovered in the late 1940s for the treatment of gram-negative infections. After several years of clinical use, its popularity diminished because of reports of significant nephrotoxicity and neurotoxicity. Recently, the antibiotic has resurfaced as a last-line treatment option for multidrug-resistant organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The need for antibiotics with coverage of these gram-negative pathogens is critical because of their high morbidity and mortality, making colistin a very important treatment option. Unfortunately, however, resistance to colistin has been documented among all three of these organisms in case reports. Although the exact mechanism causing colistin resistance has not been defined, it is hypothesized that the PmrA-PmrB and PhoP-PhoQ genetic regulatory systems may play a role. Colistin dosages must be optimized, as colistin is a last-line treatment option; in addition, suboptimal doses have been linked to the development of resistance. The lack of pharmacokinetic and pharmacodynamic studies and no universal harmonization of dose units, however, have made it difficult to derive optimal dosing regimens and specific dosing guidelines for colistin. In critically ill patients who may have multiorgan failure, renal insufficiency may alter colistin pharmacokinetics. Therefore, dosage alterations in this patient population are imperative to achieve maximal efficacy and minimal toxicity. With regard to colistin toxicity, most studies show that nephrotoxicity is reversible and less frequent than once thought, and neurotoxicity is rare. Further research is needed to fully understand the impact that the two regulatory systems have on resistance, as well as the dosages of colistin needed to inhibit and overcome these developing patterns.
Pharmacotherapy 12/2010; 30(12):1279-91. · 2.90 Impact Factor
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ABSTRACT: Chronic lymphocytic leukemia (CLL) is a slow-growing hematologic malignancy and the most common type of leukemia in the western world. The lifetime risk for developing CLL is 1 in 216 men and women. Unfortunately, CLL is considered incurable with the chemotherapeutic agents available today. Bendamustine is a new agent that was recently added to the available regimens for the treatment of CLL. It was also recently approved for the treatment of non-Hodgkin's lymphoma. Its mechanism of action is unknown, but it contains an alkylating group similar to that of other bifunctional alkylating agents such as chlorambucil, and it also contains a benzimidazole central ring thought to exhibit antipurine-like properties. The United States Food and Drug Administration approved bendamustine based on results from an international phase III study of CLL in which bendamustine was compared with chlorambucil in treatment-naïve patients. Ongoing clinical trials are assessing the utility of bendamustine in combination with other agents for the treatment of CLL, as well as for other malignancies.
Pharmacotherapy 11/2009; 29(11):1375-84. · 2.90 Impact Factor
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ABSTRACT: Cardiotoxicity is an emerging concern with a new class of drugs known as targeted agents, which include trastuzumab and sunitinib. Sunitinib is a small molecule that inhibits multiple tyrosine kinase receptors. This drug was approved by the United States Food and Drug Administration in 2006 for the treatment of clear cell metastatic renal cell carcinoma and advanced gastrointestinal stromal tumors. We describe a 65-year-old woman who was treated with sunitinib for metastatic clear cell renal cell carcinoma. After 5 months of therapy, she developed acute heart failure requiring hospitalization; sunitinib was immediately discontinued. The patient had classic symptoms of heart failure, including pleural effusion. An echocardiogram revealed a left ventricular ejection fraction of 30%. She received standard treatment for heart failure, including a beta-blocker, an angiotensin-converting enzyme inhibitor, and diuretics. Within 1 month, the patient's symptoms resolved, and subsequent cardiac evaluation showed that her left ventricular ejection fraction returned to normal. According to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute, her cardiac event associated with sunitinib was defined as grade III toxicity. One month later, sorafenib, another tyrosine kinase inhibitor, was started with the aim of continuing her previous response to sunitinib. After 7 months of sorafenib therapy, the patient had no evidence of heart failure, and her condition was responding to treatment. Clinicians should be aware that sunitinib-induced heart failure occurs occultly and that many--but not all--cases resolve with discontinuation of the drug. Use of sorafenib after sunitinib-induced heart failure appears to be safe and effective, which suggests that cardiotoxicity is not a general class effect of the tyrosine kinase inhibitors.
Pharmacotherapy 05/2009; 29(4):473-8. · 2.90 Impact Factor
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Anthony Jarkowski
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ABSTRACT: A case of ifosfamide-induced neurotoxicity after the addition of aprepitant to an antiemetic regimen is reported.
A 24-year-old white man diagnosed with a malignant peripheral nerve sheath tumor initially in the late 1990s was admitted to the hospital for treatment of a recurrence of the tumor in the supra-clavicular region. In the previous five cycles of ifosfamide, carboplatin, and etoposide, the patient had no problems with the neurotoxic adverse effects associated with ifosfamide use. With the fifth cycle of therapy, the patient suffered severe nausea and vomiting that required his readmission to the hospital. With the initiation of the sixth cycle of chemotherapy, aprepitant was added to the existing antiemetic regimen of ondansetron and dexamethasone. During the sixth cycle, approximately six hours after the infusion of ifosfamide on day 3, the patient exhibited the classic symptoms of ifosfamide-induced neurotoxicity, including visual and auditory hallucinations, obvious sleepiness, confusion, and delirium. Since his symptoms resolved by morning, it was determined that the patient did not require treatment with methylene blue. With the initiation of the seventh cycle of chemotherapy, aprepitant was again added to the standard antiemetic regimen of a corticosteroid and serotonin receptor antagonist. During this hospitalization, around-the-clock methylene blue was added to prevent neurotoxicity. The patient tolerated chemotherapy well without any signs or symptoms of neurotoxicity and was discharged four days later.
A 24-year-old patient treated with ifosfamide, carboplatin, and etoposide for a malignant peripheral nerve sheath tumor developed ifosfamide-induced neurotoxicity after the addition of aprepitant to a standard antiemetic regimen consisting of ondansetron and dexamethasone.
American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 01/2009; 65(23):2229-31. · 2.10 Impact Factor
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ABSTRACT: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder arising from a single genetic mutation that leads to an increase in immature myeloid cells in the bone marrow and the accumulation of these cells in the blood. Typically, CML represents 15-20% of all adult leukemias, with 4830 new cases expected in 2008. The cytogenetic hallmark of CML is the Philadelphia chromosome, which is the result of the reciprocal translocation and conjugation of the breakpoint cluster region (BCR) gene, BCR, on chromosome 22 and the Abelson (ABL) kinase gene, ABL, on chromosome 9. Current treatment is aimed at inhibiting BCR and ABL kinase with novel agents, the first being imatinib in 2003, and more recently dasatinib in 2006. Nilotinib is a new small-molecule inhibitor of tyrosine kinase rationally developed from the crystalline structure of the imatinib-ABL complex. It represents an aminopyrimidine derivative of imatinib with approximately 30 times more potency in vitro against imatinib-sensitive BCR-ABL-expressing cell lines and activity against 32 of 33 point mutations conferring resistance to imatinib. Data from phase I and II studies show that nilotinib has activity against all phases of CML in patients who are intolerant or have failed therapy with imatinib or dasatinib. Nilotinib represents a new therapeutic option for patients with CML who are intolerant or have failed therapy with imatinib. Ongoing clinical trials are assessing nilotinib's role in the treatment of patients with newly diagnosed CML and its long-term efficacy and safety.
Pharmacotherapy 12/2008; 28(11):1374-82. · 2.90 Impact Factor
