Journal of Oncology Pharmacy Practice

Objective: The opportunity to apply a sampling plan was evaluated. Costs were computed by a microcosting study.

Setting: In 2003, a sampling plan was defined to reduce the number of chemotherapy quality controls while preserving the same level of quality. Recent qualitative and quantitative changes led us to define a second sampling plan supplemented by an economic evaluation to determine the cost and cost-savings of quality control.

Methods: The study considers preparation produced during four semesters classified into three groups. The first one includes drugs produced below 200 batches a semester. Group 2, those for which the lot of preparation lots would have been rejected twice among these four semesters. Group 3, those would have been accepted (≥3 ‘acceptable lot’). A single sampling plan by attributes was applied to this group with an acceptance quality level of 1.65% and a lot tolerance percent defective below 5%. A micro-costing study was conducted on quality control, from the sampling to the validation of the results.

Results: Among 39 cytotoxic drugs, 11 were sampled which enabled to avoid a mean of 17,512 control assays per year. Each batch of the 28 non-sampled drugs was however analyzed. Costs were estimated at 2.98€ and 5.25€ for control assays depending of the analytical method. The savings from the application of the sampling plans was 153,207€ in 6 years.

Conclusion: The sampling plan allowed maintaining constancy in number of controls and the level of quality with significant costsavings, despite a substantial increase in drugs to assay and in the number of preparations produced.

Objectives: This cost-efficiency analysis of the granulocyte colony-stimulating factors (G-CSF) filgrastim (originator Neupogen® and biosimilar Zarzio®) and pegfilgrastim (Neulasta®) examined against a time horizon of 1–14 days of treatment and across the European Union G5 countries (a) when, cost-wise, using Neulasta® 6 mg versus Neupogen® or Zarzio® 300 µg may be cost-saving in reducing the incidence of chemotherapy-induced febrile neutropenia; and (b) if cost-wise, treatment with Zarzio® 300 µg yields a savings advantage over Neupogen® 300 µg.

Methods: Cost-efficiency analysis of the direct costs a buyer or payer would incur when purchasing or covering any of these agents for managing one patient during one cycle of chemotherapy under regimens of 1–14 days of standard filgrastim using the population-weighted average unit dose cost of each agent per their public pack cost across the European G5 countries.

Results: The cost of Neupogen® treatment ranged from €128.16 (1 day) to €1794.30 (14 days), compared to €95.46 and €1336.46 for Zarzio®, thus yielding potential cost savings from €32.70 to €457.84 for the latter. Neulasta® turns cost-saving at day 12 of Neupogen® treatment. At no point over a 14-day treatment period did Neulasta® yield a savings advantage over Zarzio®.

Conclusion: Prophylaxis or treatment of febrile neutropenia with Zarzio® is cost-efficient under all possible treatment scenarios relative to Neupogen® and to Neulasta®. In the absence of convincing evidence that pegfilgrastim is pharmacotherapeutically superior to standard filgrastim, there is no cost-efficiency rationale to treat with Neulasta® over Zarzio®, though there may be a small window of approximately 3 days where Neulasta® is cost-efficient over Neupogen®. Regardless, our analysis shows Zarzio® to be the most cost-efficient approach to reducing the incidence of febrile neutropenia in chemotherapy-treated patients.

Purpose: Develop and implement a method to characterize clinical pharmacy activities and the associated medication use in a comprehensive cancer center. A standard characterization of clinical pharmacy services facilitates benchmarking and informs continuous development.

Methods: A set of quantifiable parameters to describe clinical pharmacy activities and the associated medication use was proposed and validated by peer review. For implementation, clinical pharmacy interventions for six clinical pharmacy services at the King Hussein Cancer Center in 2008 were prospectively documented and the numbers of patients and medications dispensed for the same period were obtained from the admission office and pharmacy database respectively.

Results: The method comprised four main aspects: (1) number of interventions, (2) type of interventions, (3) number of doses dispensed, and (4) the NNI which is the number of doses dispensed for one intervention to occur. A total of 8552 interventions were recorded for 37,784 patient days. Interventions were highest in the pediatric oncology and ICU with 2612 (31%) and 1867 (22%) respectively, followed by medical oncology 1563 (18%), BMT 998 (12%), palliative care 792 (9%), and surgery 720 (8%). Interventions per 1000 patient days were: ICU 555, pediatric oncology 326, BMT 319, palliative care 244, medical oncology 137, and surgery 83. Main intervention categories for all services: therapeutic 3055 (36%), safety 2195 (26%), quality assurance 2376 (28%), and education-information 925 (10%). The number of doses dispensed per 1000 patient days was: BMT 19,404, palliative care 17,272, ICU 12,290, medical oncology 13,182, pediatric oncology 12,093, and surgery 8976. Finally, NNI was as follows: ICU 22, pediatric oncology 39, BMT 60, palliative care 71, medical oncology 96, and surgery 109.

Conclusion: A method for characterizing clinical pharmacy interventions and medication use was developed and used to compare different oncology clinical pharmacy services. Further work is warranted to refine and validate the parameters proposed.

Nitric oxide (NO) is involved in different stages of malignancies. Increased levels of NO have been reported in different leukemias. Imatinib is the preferred drug for the treatment of chronic myeloid leukemia (CML). Turmeric powder contains curcumin which has anti-leukemic property and also decreases NO synthesis. This study was conducted on fifty patients of CML divided into two groups, group A receiving imatinib alone and group B receiving turmeric powder along with imatinib for six weeks. Nitric oxide levels were estimated in these patients before and after receiving therapy and were analyzed statistically. Nitric oxide levels were found to be significantly decreased in both the groups, but more significantly in group B after receiving the respective treatments. Thus, curcumin acts as an adjuvant to imatinib in decreasing the NO levels and may help in the treatment of CML patients.

Purpose: Evaluation of containment safety devices designed and introduced to protect preparers and administrators of hazardous drugs, through a multiple-test assessment.

Methods: Six devices were compared: (1) Kis1 gravity-fed infusion set (Doran International, France), (2) Tevadaptor Spike Port Adapter (Teva Pharma AG, France), (3) Phaseal Infusion Adapter C100 (Carmel Pharma AB, France), (4) Codan Connect Z (Codan, France), (5) Pchimx with or without a cap (Doran International, France), and (6) Clave extension set 011-H1225 with or without Spiros (Hospira, France). Assessment of exposure to hazardous drugs was performed using quinine as fluorescent marker. Mechanical tests included tightness, tension tests, and estimation of the force required to connect the infusion device to the bag. Ergonomic tests were performed by six pharmaceutical technicians. Microbiological contamination was tested with media-fill, on connected bag.

Results: No cytotoxic contamination was detected when using Phaseal, Tevadaptor or the Clave extension set with Spiros, Pchimx with a cap or Connect Z devices. For mechanical tests, all devices complied with the norm. Microbiological growth was observed neither in bags nor in tubings. The ergonomic study revealed differences between the devices for potential cytotoxic contamination risk only, but not for handling.

Conclusions. The use of containment safety devices offers improved handling conditions of hazardous compounds. As this study takes various selection criteria into account, its results offer assistance in choosing the most suitable device.

Purpose: Cyclophosphamide (CP) contamination has been detected in Japanese hospitals. In other countries, the surface contamination of CP vials has been reported; however, the manufacturing process of Japanese CP vials is unknown, so the conditions are not necessarily the same as in other countries. This study aimed to establish whether vial surface contamination also occurs in Japan.

Method: Contamination of vial surfaces was examined with a wipe test. Urine samples were taken from a pharmacist, engaged solely in dispensing work, for 29 h. It was also investigated whether CP vials were dispensed during the urine sampling period. In addition, vial surfaces, purposely coated with CP and then washed, were examined using wipe tests.

Result: CP was detected at 30–60% in vials, which was 11–62 ng (0.10–0.54 ng/cm²). One of the urine samples was contaminated (CP 13.5 ng); this was taken on Day 2 (11:35 AM). CP was not detected among the washed vials.

Discussion: This study shows that the surface of Japanese CP vials was contaminated and that it was probable that healthcare workers were exposed to CP. CP absorption by the pharmacist was probably due to dermal uptake while dispensing. Washing the vial is considered effective to avoid CP exposure. Manufacturers should be more proactive to prevent contamination and healthcare workers should comply with exposure prevention rules. Cytotoxic drugs should be included in institution monitoring lists.

Aims and background: At the Oncology Department of the Chieti and Ortona Hospitals, the pharmacist designated by the Abruzzo Region to oversee the obligatory monitoring of innovative oncological drugs listed in the database of the Italian Medicines Agency (AIFA) collaborates with oncologists to educate them about evidenced-based prescribing for off-label uses of drugs and to optimize the efficiency of spontaneous reporting of adverse drug reaction (ADR) local system.

Methods: The contribution of the pharmacist as a member of the healthcare team was evaluated using the following indices: the percentage of off-label prescriptions of the innovative drugs monitored, the number of reported ADRs, and the percentage of pharmacist suggestions actually implemented by physicians.

Results: In the course of 3 years (2008–2010), the pharmacist monitored a total of 843 patients treated with 716 appropriate uses and 127 off-label uses of drugs, oversaw a reduction in the latter from 28.3% in 2008 to 9.6% in 2010, and contributed to almost tripling the number of reported ADRs, from 10 in 2008 to 27 in 2010. In 2010, the pharmacist identified 60 potentially inappropriate prescribing cases, and proposed more appropriate prescriptions for each case: 68.3% (41) of the suggestions were implemented by the physicians and only 31.7% (19) were not. According to answers to a questionnaire administered at the end of the 2010 to evaluate the usefulness of this particular collaboration, physicians are interested in continuous and extensive collaboration.

Conclusions: This article demonstrates that a pharmacist, active in the department as part of the heath-care team, can facilitate evidenced-based prescribing for off-label uses of drugs and improve spontaneous reporting of ADRs.

Purpose: The aim of this study was to investigate the physicochemical stability of clofarabine (CAFdA) injection concentrate and ready-to-use CAFdA infusion solutions over a prolonged period of 28 days.

Methods: To determine the stability of CAFdA infusion solutions, the injection concentrate (Evoltra®, 1 mg/mL, Genzyme) was diluted either with 0.9% sodium chloride or 5% glucose infusion solution. The resulting concentrations of 0.2 mg/mL or 0.6 mg/mL, respectively, were chosen to represent the lower and upper limit of the ordinary concentration range. Test solutions were stored under refrigeration (2–8°C) or at room temperature either light protected or exposed to light. CAFdA concentrations and pH values were determined at different time intervals throughout a 28-day storage period. Compatibility of diluted CAFdA infusion solutions (0.1–0.4 mg/mL) with different container materials (polyvinyl chloride (PVC), glass, and polypropylene/polyethylene (PP/PE)) was tested over a 48-h storage period. CAFdA concentrations were measured by a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection.

Results: CAFdA injection concentrate and CAFdA infusion solutions remained physicochemically stable (>90% CAFdA) for 4 weeks. Results are independent of storage conditions, drug concentrations (0.2, 0.6, and 1.0 mg/mL) and diluents (0.9% sodium chloride, 5% glucose infusion solution). Adsorption of CAFdA to container material can be excluded.

Conclusions: CAFdA injection concentrate and diluted infusion solutions in commonly used vehicles are stable for at least 28 days either refrigerated or at room temperature. Physicochemical stability favors pharmacy-based centralized preparation. Due to microbiological reasons, strict aseptic handling and storage of the products under refrigeration is recommended.

Purpose: DC Bead™ is successfully used for chemoembolization of various liver cancers. The purpose of this study was todetermine the loading capacity of the semi-synthetic topoisomerase-1 inhibitor topotecan into the DC Bead™ microspheres under static or agitated conditions and to assess the physicochemical stability over a period of 7 days.

Methods: Commercially available topotecan hydrochloride powder (Hycamtin®) was reconstituted with water for injection to yield a nominal concentration of 1 mg/mL topotecan. Polyvinyl alcohol (PVA)-based microspheres (DC Bead™, 300–500 µm, 2 mL/vial) were mixed with 4 mL of the reconstituted topotecan solution. Vials were stored light protected at room temperature under static or agitated conditions for 7 days (n = 3, for each loading condition). At different time intervals, samples were taken from the excess solution and assayed via a stability-indicating HPLC assay. Drug-loading profiles were determined by measuring the remaining topotecan concentration in the excess solution.

Results: Under agitated conditions, topotecan was loaded into the microspheres rapidly after mixing. After 5 min 86.4 ± 0.1% of topotecan was loaded. Under static conditions, drug uptake was slower. Only 65.0 ± 0% were loaded after 5 min; 86.6 ± 0.1% drug uptake was achieved not until 1 h. Over a storage period of 7 days, topotecan remained loaded in the DC Bead™ microspheres at a level of >90%.

Conclusion: Drug uptake of 4 mg topotecan (1 mg/mL solution) into DC Beads™ was faster under agitated loading conditions. Nevertheless, after 1 h, ∼90% of topotecan was loaded into the DC Bead™ microspheres independent from the type of loading condition. The loading rate remained >90% over the observation period of 7 days and light-protected storage at room temperature. Loading and stability of topotecan-loaded DC Beads™ is suitable and convenient for preparation in a pharmacy-based cytotoxic preparation unit.

Background: Radiotherapy with concomitant and adjuvant temozolomide has been the standard of care for newly diagnosed glioblastoma in adults since the pivotal trial by Roger Stupp and colleagues. The effectiveness of this regimen has not been evaluated in Canada. Additionally, the impact of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation on patient survival has not been confirmed. Hence, survival outcomes and MGMT predictive value were compared for the patients in Alberta versus the Stupp trial population.

Methods: Retrospective chart review of 215 adult glioblastoma patients who started radiotherapy and temozolomide between January 2007 and December 2010 at the Cross Cancer Institute (Edmonton, Alberta) or the Tom Baker Cancer Centre (Calgary, Alberta).

Results: In the Alberta population, median overall survival was 14.3 months (vs. 14.6 months in trial, p = NS) and median progression-free survival was 5.8 months (vs. 6.9 months in trial, p = NS). However, unlike the trial, the Alberta MGMT subgroup analysis for overall survival was not statistically significant, despite a hazard ratio of 0.65 in favor of the methylated group. More Alberta patients received corticosteroids (p < 0.0001) and fewer underwent complete resection (p = 0.0001) or a postprogression second surgery (p = 0.01) than the Stupp population, but characteristics were otherwise similar.

Conclusion: Current practice in Alberta enables patients to achieve overall and progression-free survival similar to the clinical trial. Further follow-up is required to confirm the predictive value of the MGMT assay. Until that is clarified or better treatments are developed, it is reasonable to continue offering this treatment regimen to patients regardless of MGMT methylation status.

Purpose: Hydration and urinary alkalinization are essential for reducing renal dysfunction with high dose methotrexate (HDMTX). This report presents an analysis of institutional methods used to achieve adequate urinary alkalinization and output for patients receiving single agent HDMTX. Renal and metabolic parameters of tolerance were examined.

Methods: Medical records of adult patients receiving HDMTX during the calendar years of 2008–2009 were retrospectively reviewed to determine the time to achieve urine pH > 7. Number of hospital days, bicarbonate dose, ordered hydration rate, urine output, and urine pH were assessed. A survival analysis model was run for time to urine pH > 7 using preadmission oral bicarbonate as a predictor variable and including a frailty term. Observational statistics were performed for other parameters.

Results: The analysis included 79 encounters for ten patients. Urine pH > 7 was achieved more rapidly in patients receiving preadmission oral bicarbonate (P = 0.012). The number of patients receiving HDMTX on the same day as admission was greater for those receiving preadmission oral bicarbonate (47%) in comparison to those who did not (2%), and they spent less time in the hospital. A standard regimen for hydration and urinary alkalinization based on this project is reported. The nature and frequency of adverse events were as expected for this treatment.

Conclusion: At our institution, the time to achieve urinary alkalinization was reduced for patients receiving preadmission oral bicarbonate which facilitated chemotherapy infusion on the same day as admission and decreased the number of calendar days that patients stayed in the hospital.

Purpose: The purpose of this review article is to describe the recent data supporting the use of epidermal growth factor receptor (EGFR) receptor tyrosine kinase inhibitors (TKIs) in the first-line setting of EGFR mutation-positive non-small cell lung cancer (NSCLC).

Summary: EGFR receptor TKIs were originally developed in unselected NSCLC patients and demonstrated modest clinical benefit compared to placebo. With the discovery of improved benefits in the approximately 16% of NSCLC patients with an EGFR mutation, trials in selected populations were undertaken, demonstrating comparable efficacy to standard chemotherapy with an improved toxicity profile. The most common toxicity is rash, sometimes requiring dose adjustment and discontinuation and the most serious toxicity is interstitial lung disease, which occurs in about 1% of patients treated with EGFR receptor TKIs and is fatal in 30% who develop this toxicity.

Conclusion: The EGFR receptor TKIs are an effective therapy in EGFR-mutated NSCLC and are recommended as first-line therapy for those with advanced or metastatic disease.

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 sources: 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.

The incidence of second malignancies was shown to be increased in patients with multiple myeloma. Although a shared genetic predisposition or common environmental carcinogens may account for the occurrence of both myeloma and additional cancers, multiple immune defects encountered in myeloma might play an important role in this regard. This review explores the impairments in both cellular and humoral mediated immunity in multiple myeloma, linking them with increased susceptibility to infections and additional cancers. In addition, the recent therapeutic advances transformed myeloma into a chronic entity, with multiple relapses and salvage therapies, which may result in cumulative immunosuppression. Although recent reports have suggested an increased rate of second cancers in myeloma patients treated with lenalidomide, the true impact of this agent and other novel anti-myeloma therapies on the incidence of additional malignancies remains to be clarified.

Current anticoagulation guidelines for cancer patients are largely based upon studies done in the general population. Anticoagulation studies in cancer patients with venous thromboembolism (VTE) have compared varying doses of different low molecular weight heparins (LMWH) to warfarin or unfractionated heparin (UFH) regimens, and most guidelines recommend LMWH as the preferred agent over vitamin K antagonists. However, very few studies compare different dosing regimens of the LMWH itself. As a result, practitioners attempt to extrapolate results from studies done in the general medicine population and apply them to cancer patients with VTE. Considering the differences in risk factors and hypercoagulability between these populations, such generalizations may compromise outcomes or safety for cancer patients. Currently, no study to date has compared the safety and efficacy of enoxaparin 1.5 mg/kg subcutaneously (SC) once daily vs. 1 mg/kg SC twice daily in a prospective, randomized fashion, for the longterm treatment of VTE in patients with cancer. The purpose of this article is to review currently available literature utilizing these dosing schemes in order to risk-stratify cancer patients who may better qualify for one dosing regimen as compared to the other. Our analysis suggests that enoxaparin dosed at 1.5 mg/kg SC once daily may be a safe and effective alternative for the treatment of VTE in cancer patients with both a low risk of recurrent VTE and bleeding. In the absence of additional studies, the dosing of enoxaparin for cancer patients should be based on patient-specific risk factors.

Purpose: The purpose of this review article is to describe the emerging data of ALK receptor tyrosine kinaase inhibitors in ALK mutation positive NSCLC.

Summary: ALK mutations have been identified in approximately 2.4–13% of patients with NSCLC, occurring more frequently in adenocarcinomas and never and light smokers. Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations. A phase II study demonstrated an overall response rate of 57% (95% CI, 46 to 68), with the most common toxicity grade I fatigue and visual disturbances. Elevations in lever function tests were also reported.

Conclusion: The ALK receptor tyrosine kinase inhibitor crizotinib may be an effective therapy in ALK mutated NSCLC and is currently being compared to standard chemotherapy for advanced or metastatic NSCLC.

Purpose: The pharmacology, pharmacokinetics, clinical trials, adverse effects, dosage, and economic considerations of pralatrexate (PDX) are reviewed.

Summary: Peripheral T-cell lymphoma (PTCL) comprises approximately 15–20% of all aggressive lymphomas and 5–10% of all non-Hodgkin’s lymphomas. Advanced PTCL is often refractory to traditional first-line chemotherapy regimens. PDX was developed as a synthetic folate analog antimetabolite that competitively inhibits dihydrofolate reductase (DHFR). This results in the depletion of thymidine, leading to interference with deoxyribonucleic acid synthesis and cancer cell death. PDX has a higher potency than methotrexate and edatrexate (EDX). The efficacy and safety of PDX have been demonstrated in the PROPEL trial, a prospective phase II trial in patients with relapsed or refractory PTCL. Patients with prior stem cell transplantation receiving PDX also had similar response rates (RRs). PDX was investigated on the treatment of relapsed or refractory cutaneous T-cell lymphoma, previously treated advanced non-small cell lung cancer and other solid malignancies. PDX has similar side effects to other DHFR inhibitors. The most common side effect of PDX is mucositis. The recommended dose of PDX is 30 mg/m² weekly once for 6 weeks in 7-week cycle until disease progresses or unacceptable toxicity for PTCL and may require dose reduction or discontinuation. Patients should be supplemented with oral folic acid and intramuscular vitamin B₁₂ injections.

Conclusion: PDX provides clinical benefit to patients with relapsed or refractory PTCL with durable complete and partial responses in patients who had not responded to multiple prior treatment regimens.

Lenalidomide is a derivative of thalidomide and is FDA-approved for the treatment of myelodysplastic syndrome and, in combination with dexamethasone, for the treatment of relapsed multiple myeloma. Pulmonary toxicity with thalidomide is a recognized potential complication; however, there have only been two case reports in the literature of lenalidomide-associated pulmonary toxicity. In this case, we describe a patient who developed profound dyspnea, decreased exercisetolerance, and new ground-glass opacities with reticulation, consistent with a nonspecific interstitial pneumonia pattern. Clinical suspicion for pulmonary drug toxicity was high and lenalidomide was discontinued. Within 2 weeks of stopping lenalidomide, the patient had significant improvement in dyspnea and interstitial changes on CT were resolving. After 8 weeks, there was complete resolution of symptoms. Lenalidomide-induced pulmonary toxicity is significantly debilitating but, to date, it appears to be reversible with discontinuation of the medication.

A 57-year-old man with metastatic melanoma developed grade 4 thrombocytopenia during treatment with ipilimumab (anti-CTLA-4 antibody). Bone marrow examination confirmed increased megakaryocytes, which supported a diagnosis of drug-induced, immune-mediated thrombocytopenia and he received 1 mg/kg prednisolone and 1 g/kg intravenous immunoglobulin. There was a delayed response to treatment, with the first evidence of rise in platelet count seen after 9 days. This was followed by a complete and sustained resolution of thrombocytopenia. Hematological toxicity has rarely been associated with ipilimumab and to our knowledge this is the first report of isolated grade 4 thrombocytopenia. This case demonstrates the importance of monitoring full blood count in all patients receiving ipilimumab.

Pneumocystis jirovecii (formerly carinii) pneumonia (PJP) is an opportunistic infection well-recognized in patients with profound T cell immunodeficiency. It is much less common in patients with solid tumors unless they have other major predisposing factors such as prolonged treatment with corticosteroids or T4 lymphocyte counts of less than 200 cells/mm³. We present a previously unreported case of fatal PJP in a breast cancer patient with bone metastases who was receiving a first-line treatment with weekly paclitaxel, trastuzumab, and dexamethasone as premedication for paclitaxel. She had received eight doses of paclitaxel at 80 mg/m², trastuzumab 2 mg/m², and dexamethasone 10 mg for just over 7 weeks when she was diagnosed with PJP. While the patient’s granulocyte counts were normal throughout her treatment, the total lymphocyte counts reached the nadir of 400 cells/mm³ a few days after the eighth dose of chemotherapy – around the time of PJP diagnosis. Both dexamethasone and the total lymphocyte nadir predisposed this patient to PJP.

Anaphylaxis related to drug therapy with 5-HT3 antagonists, in particular, palonosetron has not been reported frequently in the literature. Here a case is presented where the patient possibly had an anaphylactic reaction to palonosetron. In this case report, a 40-year-old female with ovarian cancer developed shortness of breath and hypotension after receiving her palonosetron as part of her premedication for chemotherapy. The patient recovered successfully with fluids and supportive care. This case demonstrates that even after successful treatment in the past with palonosetron a patient may later develop a hypersensitivity to the agent.

Gemcitabine is a commonly used chemotherapeutic agent for a variety of tumors. Although this nucleoside analog antineoplastic agent is similar in structure to cytarabine, central nervous system toxicities have rarely been attributed to gemcitabine. The posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible neurological and radiological findings that has been associated with use of chemotherapeutic and more recently novel targeted therapies. We describe one case of a 41-year-old woman with PRES under treatment for leiomyosarcoma because of the probable association with gemcitabine. Our case, to our knowledge, represents the seventh published report of this particular toxicity. Naranjo algorithm, efficacious method for assessing the causality of adverse drug reactions (ADRs) from a case report, suggests a direct casual relationship. PRES is probably a rare complication of gemcitabine, but the oncologist should take it into careful consideration, because PRES is reversible with treatment of current hypertension or removal of the causative agent. However, failure to quickly recognize the syndrome and discontinue the offending agent may result in profound and permanent central nervous system dysfunction or death.

Imatinib mesylate is a drug that has been approved for treatment of advanced gastrointestinal stromal tumors (GISTs) and patients with leukemia such as chronic myeloid or Philadelphia chromosome-positive acute lymphoblastic. Although it has been described only in one patient with testicular hydrocele and gynecomastia in the literature, several cases of male gynecomastia have been reported with the use of imatinib mesylate in chronic myeloid leukemia (GML). Generally, male mastoplasia resolves after discontinuation of imatinib treatment. We report a 73-year-old male with metastatic GISTs who developed gynecomastia and unilateral testicular hydrocele while receiving imatinib mesylate. Nine months after commencing imatinib treatment, gynecomastia and testicular hydrocele were determined. Hormone analyses requested showed serum testosterone levels below and serum estrogen levels above normal limits. During the first month after discontinuing imatinib mesylate treatment, serum testosterone level was normal and there was a partial regression in gynecomastia and testicular hydrocele. To our knowledge, this is the second report of male gynecomastia following imatinib mesylate treatment of a patient with GIST. In conclusion, male patients who are to receive treatment with imatinib mesylate may be monitored for serum testosterone levels and for other reproductive hormone profiles before initiation of the treatment and their breasts may be examined during follow-up visits.

A number of chemotherapy drugs are well known to cause various histopathologic patterns of lung injury. The incidence of chemotherapy-induced infiltrative pneumonitis is rare and the diagnosis is difficult due to the nonspecific clinical and radiological presentations. However, it can cause significant morbidity and mortality in cancer patients. There is no consensus on the treatment of this adverse event, but prompt diagnosis and intervention is important as fatal outcomes have been reported. We present five cases of chemotherapy-induced infiltrative pneumonitis in breast cancer patients involving docetaxel, paclitaxel, gemcitabine and cyclophosphamide.

Capecitabine administration has been associated with various allergic reactions including acneiform skin rash, linchenoid photosensitive eruption, exudative non healing scalp, skin reactions, pyogenic granuloma, subacute cutaneous systemic lupus erythematosus, exudative hyponychia dermatitis, and hand–foot syndrome. A patient who developed ventricular fibrillation following capecitabine-induced coronary vasospasm and necessitating cardioverter-defibrillator implantation was published recently in J Oncol Pharm Practice. The authors attributed this reaction to capecitabine cardiotoxicity, but capecitabine hypersensitivity is closely associated with Kounis syndrome. Tests and measures which will help to confirm, prevent and treat cardiac hypersensitivity to antineoplastic agents are recommended.