Stability of cisplatin, doxorubicin, and mitomycin combined with loversol for chemoembolization.

OBJECTIVE: To evaluate the chemical stability of a mixture of cisplatin 10 mg/mL, doxorubicin 5 mg/mL, and mitomycin 1 mg/mL in sodium chloride 0.9% (NS), and sodium chloride 0.9% and ioversol 68% (NSI). METHODS: The agents were reconstituted with NS and NSI in two groups. One syringe was made and stored protected from light at 4, 25, and 37 degrees C. Triplicate HPLC determinations were performed on each syringe at each time period. Drug concentration at T0, 4, 12, 24, 72, and 120 hours were recorded. RESULTS: Cisplatin in NS remained stable for five days at all three temperatures and lost 12.7% at 37 degrees C in 120 hours in NSI. Doxorubicin in NS remained stable throughout the five days at 4 and 25 degrees C, but lost 13.1% at 37 degrees C in 24 hours. Doxorubicin in NSI remained stable for five days at 4 degrees C and lost 16.3% at 25 degrees C by day 5, and 18.8% at 37 degrees C in 24 hours. Mitomycin in NS lost 15.8% at 4 degrees C within 24 hours, and 24.7% at 25 degrees C and 36% at 37 degrees C within four hours. Mitomycin in NSI was stable for 72 hours at 4 degrees C, 24 hours at 25 degrees C, and less than four hours at 37 degrees C. CONCLUSIONS: These agents in NS are stable for 12 hours at 4 degrees C. In NSI, they are stable for 72 hours at 4 degrees C.

Overview of hypercalcemia of malignancy.

The etiology, pathophysiology, and diagnosis of hypercalcemia associated with malignant diseases are discussed. In humans, calcium is controlled by three mechanisms: parathyroid hormone, which regulates bone resorption and renal reabsorption of calcium; calcitonin, an antagonist of parathyroid hormone; and cholecalciferol, which regulates calcium absorption from the gastrointestinal tract. Hypercalcemia of malignancy (HCM) results primarily from increased bone resorption by osteoclasts and, to a lesser extent, from increased renal tubular reabsorption. In most tumors, parathyroid hormone-related protein (PTHrP) is the primary mediator of calcium. PTHrP stimulates increased bone resorption by osteoclasts. This stimulation also activates transforming growth factor-beta (TGF-beta), which stimulates tumor cells, thus perpetuating the cycle. Hypercalcemia is usually defined as a serum calcium concentration greater than 12 mg/dL, corrected for the serum albumin concentration. In diagnosing HCM, it is important to rule out other causes of hypercalcemia, such as primary hyperparathyroidism.

Onycholysis associated with weekly administration of paclitaxel.

OBJECTIVE: To report an unusual reaction associated with weekly administration of paclitaxel. CASE SUMMARIES: Onycholysis was seen in four women with recurrent ovarian cancer being treated with low-dose, weekly paclitaxel. Two of the patients had previously received higher doses of paclitaxel on an every-three-week schedule without similar reactions. Onycholysis developed between weeks 10-13 of treatment in three of the patients. In the fourth patient, it developed shortly after initiation of weekly paclitaxel. None of the reactions required dose adjustments or discontinuation of therapy. Direct toxicity to the nail bed or inhibition of angiogenesis are possible mechanisms for this reaction. DISCUSSION: Onycholysis, separation of the nail from the nail bed, is an infrequent adverse effect of drug therapy. Antineoplastic drugs have previously been reported to cause onycholysis, pigmentation, bands, thickening or thinning of the nail bed, and nail shedding. Nail changes with the taxanes, primarily docetaxel, are reported in up to 30-40% of patients. Paclitaxel is not commonly associated with dermatologic reactions, although localized skin reactions and tissue necrosis have been reported. Nail changes, pigmentation or discoloration of the nail bed, occur in 2% of patients receiving paclitaxel. CONCLUSIONS: Onycholysis is an uncommon reaction that may occur in some patients receiving weekly, low-dose paclitaxel therapy. The reaction is not life-threatening and does not warrant discontinuation of therapy. However, clinicians should be aware of the possibility of this effect and be prepared to advise patients who develop signs of nail changes.

Pharmacy staff interventions in a medical center hematology-oncology service.

OBJECTIVES: Many pharmaceutical care efforts remain undocumented, resulting in underestimation of the importance of the pharmacy staff interventions and missed opportunities to find new directions for quality improvement. The purpose of this project was to document and analyze the pharmaceutical care interventions of the staff of a hematology-oncology pharmacy. DESIGN: Interventions were self-reported by pharmacy staff members. The data collection period was October 1, 1995, to May 31, 1996. Intervention analysis consisted to types of interventions performed, categories of personnel performing interventions, intervention acceptance rate by staff physicians, and medication cost avoidance. PARTICIPANTS: This project was performed by the Hematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed Army Medical Center, Washington, D.C. SETTING: Walter Reed Army Medical Center, Washington, DC, a 1,000-bed teaching and research institution of the U.S. Army Medical Department. RESULTS: Pharmacy staff reported 503 interventions. The leading categories of interventions were clinical consultations (167), correction of prescribing errors (85), and patient treatment procedures (65). The interventions were primarily initiated by oncology pharmacists and residents (68.8%) and oncology pharmacy technicians (30.6%). The intervention acceptance rate was 97%. Medication cost avoidance was $23,091. CONCLUSION: A significant amount of pharmaceutical care was documented by the hematology-oncology pharmacy staff, with both oncology pharmacists and oncology pharmacy technicians making key contributions. The pharmacy staff's interventions had a high rate of acceptance by the medical and nursing staffs, and resulted in significant medication cost avoidance.

Acute pancreatitis associated with continuous infusion cytarabine therapy: a case report.

BACKGROUND: While acute pancreatitis is a recognized complication of numerous drugs, cytarabine's role in causing this complication is controversial. Approximately 15 cases have been reported to the Food and Drug Administration linking cytarabine with pancreas-related toxicities. Previous case reports have been complicated by comorbid illnesses and the coadministration of other drugs associated with acute pancreatitis. METHODS: This report describes the clinical course of a patient with acute myelogenous leukemia (AML) who developed recurrent pancreatitis associated with cytarabine therapy. RESULTS: A male age 36 years with French-American-British M5B acute myelogenous leukemia received induction cytarabine (200 mg/m2/day) by continuous infusion for 7 days, and subsequently developed acute pancreatitis. The patient was rechallenged with intermittent, bolus, high dose cytarabine (HDAC) (3 g/m2bid administered over 3 hours) during the following intensification treatment, but did not develop clinical acute pancreatitis. Retreatment with continuous infusion cytarabine at a later time resulted in recurrence of acute pancreatitis. CONCLUSIONS: This case illustrates that cytarabine treatment may cause acute pancreatitis, and that this toxicity may be schedule dependent. In those with known sensitivity to cytarabine, altering the administration technique may avoid this complication.

Parenteral benzyl alcohol-induced hypersensitivity reaction.

An uncommon hypersensitivity reaction due to parenteral benzyl alcohol administration is reported. One patient treated with benzyl alcohol-preserved cytarabine, vincristine, and heparin solutions developed a systemic hypersensitivity reaction on three separate occasions. Hypersensitivity to benzyl alcohol was confirmed by skin testing. Clinically, the patient presented with a fever and a maculopapular rash on the chest and arms. None of the reactions were life-threatening or required hospitalization of the patient.

Doxorubicin-induced hypersensitivity reactions.

An uncommon side effect of the anthracycline antibiotics is allergic reactions. We report three patients treated with doxorubicin hydrochloride who developed systemic hypersensitivity reactions to the drug. In all three cases, the onset of the reaction coincided with the initiation of the doxorubicin, and was confirmed by rechallenge with the drug. An urticarial rash with pruritus was the primary clinical manifestation seen in all cases. All reactions responded to treatment with diphenhydramine, or diphenhydramine and hydrocortisone. None of the reactions were life-threatening or required hospitalization of the patient. In two patients, use of the drug was discontinued because of the reaction. Pretreatment with diphenhydramine, prednisone, and cimetidine may have reduced the severity of the reaction in one patient.

Toxic lesions of the hand associated with chemotherapy.

New agents used in cancer chemotherapy are continually appearing which, in turn, leads to newer patterns of toxicity. This report reviews experience with some upper extremity lesions associated with chemotherapy. Doxorubicin extravasation caused deep soft tissue necrosis that was successfully managed by aggressive excision and delayed coverage with a well-vascularized flap. Bleomycin resulted in palmar swelling, erythema, and digital pulp necrosis, which healed secondarily. Intravenous nitrogen mustard caused an immediate, and alarming, perivenous hyperpigmentation that was painless but long lasting. Bacille Calmette-Guerin immunotherapy was followed by a large, localized skin slough that was indolent, painful, and healed secondarily. 5-Fluorouracil was associated with permanent, dark pigmentation of the hands along with slough of the digital pulps. The myelosuppression resulting from combination therapy may also predispose these patients to fulminant hand infections, which can be lethal.

Aseptic technique as a safety precaution in the preparation of antineoplastic agents.

A subject of concern among personnel working in cancer chemotherapy treatment areas is the occupational hazard posed by the antineoplastic drugs. A review of the literature reveals a number of proposed safety precautions, including glove boxes, vertical air-flow hoods, masks, gloves, gowns, and routine medical examinations. The concept of using aseptic technique as a safety precaution is presented, with particular emphasis on the importance of maintaining negative pressure in vials. We also discuss the use of ultraviolet light to detect antineoplastic drug spills in a working environment and as a training and evaluation procedure.