Hiccups with high dose dexamethasone administration: a case report.

BACKGROUND: A 59-year-old male developed intractable hiccups during monthly therapy with high dose dexamethasone for multiple myeloma. Hiccups would begin hours after his first dose and continue over the 4 days of therapy. He sought assistance after his attempt at home remedies failed and the hiccups became exhausting. METHODS: The strong temporal relation between dexamethasone administration and the occurrence of hiccups indicated that dexamethasone was the cause of the patient's hiccups. Because he was responding to dexamethasone, the decision was made to continue therapy and to relieve his hiccups with metoclopramide. RESULTS: Low dose oral metoclopramide allowed the patient to continue therapy without a recurrence of the hiccups. CONCLUSIONS: Dexamethasone administration can result in intractable hiccups that persist for the duration of therapy. Low dose oral metoclopramide may prevent hiccups in patients in whom the discontinuation of dexamethasone therapy is not appropriate.

Irinotecan: a new antineoplastic agent for the management of colorectal cancer.

OBJECTIVE: To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of irinotecan, a new antineoplastic agent, and to assess its role in the treatment of colorectal and lung cancer. DATA SOURCES: English-language articles from the MEDLINE database, January 1990-March 1998; Pharmacia & Upjohn Company; published articles and meeting abstracts. STUDY SELECTION: Studies in humans with cancer, clinical case reports, and open clinical studies were reviewed. Efficacy studies were limited to trials with at least 20 evaluable patients. DATA EXTRACTION: Relevant data were extracted from published reports and abstracts. DATA SYNTHESIS: Irinotecan is an effective agent for the treatment of advanced colorectal cancer. It demonstrates significant activity as a first-line agent and in patients with disease that is refractory to fluorouracil-containing regimens. Activity against lung cancer has also been demonstrated. Limited data indicate activity against cancers of the ovary, cervix, stomach, and in non-Hodgkin's lymphomas. Major toxicity consists of myelosuppression and diarrhea. CONCLUSIONS: Irinotecan is a useful addition to the antineoplastic drug family and offers significant efficacy for treatment of patients with fluorouracil-refractory colorectal cancer.

Topotecan: a new topoisomerase I inhibiting antineoplastic agent.

OBJECTIVE: To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of topotecan, a new antineoplastic agent, and to assess its role in the treatment of cancer. DATA SOURCES: MEDLINE database English language only, January 1990-March 1998; SmithKline Beecham Pharmaceuticals; published articles, books, and abstracts. STUDY SELECTION: Studies in humans with cancer, clinical case reports, open clinical trials, and controlled clinical studies. Efficacy studies were limited primarily to trials with at least 20 evaluable patients: DATA EXTRACTION: Relevant data were extracted only from published reports. Data were obtained from studies in both articles and abstracts. Only articles written in English were reviewed. DATA SYNTHESIS: Topotecan is an effective second- or third-line therapy for patients with advanced ovarian cancer and is comparable to ifosfamide, liposomal doxorubicin, and paclitaxel. Activity in combination with other agents and as a first-line agent is yet to be determined. Limited data indicate activity in small-cell lung cancer, cancers of the breast and uterus, and in nonlymphocytic leukemia. The dose-limiting toxicity is myelosuppression. CONCLUSIONS: Topotecan is an effective second-line agent for patients with unresponsive or relapsed cancer of the ovary. It appears to be similar to other active agents in patients with this disease status. Its ultimate role in ovarian cancer and other neoplasms awaits additional evaluation in combination with other agents and as first-line therapy.

Creatine kinase elevation associated with 5-fluorouracil and levamisole therapy for carcinoma of the colon. A case report.

BACKGROUND: There have been no reports of creatine phosphokinase (CK) elevation during levamisole administration. There is only one prior report of CK elevation of noncardiac origin associated with 5-fluorouracil. METHODS: A 41-year-old man was diagnosed with Stage B2 colon carcinoma and underwent extensive surgical resection. Adjuvant therapy with 5-fluorouracil and levamisole was initiated after surgery. A complete hematologic and chemistry profile was obtained during weekly clinic visits. RESULTS: The patient's serum CK levels were normal prior to the initiation of chemotherapy but began to rise after 4 weeks of therapy, Isoenzyme analysis revealed that the CK was 100% from skeletal muscle. When the CK level surpassed 1,000 U/L, chemotherapy was discontinued. The CK levels began to decline immediately, falling to normal within 2 months. All attempts to identify a known cause of the enzyme elevation were negative. CONCLUSIONS: The temporal relationship between chemotherapy administration, enzyme elevation, and the rapid fall in enzyme levels upon discontinuation of treatment argue strongly in favor of chemotherapy as the etiology of CK elevation in the patient.

Prostate cancer: current and evolving strategies.

The staging, screening and diagnosis, and treatment of prostate cancer are discussed. Prostate cancer kills about 40,000 men in the United States each year. Signs and symptoms range from dysuria to features of advanced metastatic disease. The American Urological System of staging prostate cancer designates four stages, A through D. The tumor is graded histologically with the Gleason scale. Methods used in the screening and diagnosis of prostate cancer include digital rectal examination, the prostate-specific antigen (PSA) assay, biopsy, transrectal ultrasonography, and determination of PSA density, velocity, and age specificity. The value of screening and treatment remains controversial because tumors are generally slow-growing and conclusive data showing an effect on survival time are lacking. Treatment methods consist of prostatectomy, radiation therapy, and hormonal drug therapy or bilateral orchiectomy. The choice is influenced primarily by the stage of the disease but also by the patient's age, physical condition, and response to prior therapy. Patients with stage A or B disease are considered for prostatectomy or radiation therapy. The primary treatment for stage C disease is radiation therapy. For stage D, the main approaches are watchful waiting and bilateral orchiectomy or hormonal drug therapy to reduce androgenic stimulation of prostate tissue. Long-term survival rates are high for stages A and B and considerably lower for stages C and D. Prostate cancer responds to estrogens, but adverse effects are frequent and potentially severe. Luteinizing hormone-releasing hormone agonists (leuprolide and goserelin) are as effective as estrogens but have less toxicity; a disadvantage of these agents is an initial flaring of the disease. Other hormonal agents used include antiandrogens-progestins, flutamide, and bicalutamide. Secondary hormonal treatments (aminoglutethimide and ketoconazole) are less effective than initial hormonal therapy. Antineoplastic agents have little or no effectiveness in prostate cancer. Although the value of screening for and treating prostate cancer continues to be debated, many experts recommend annual screening for all men over 50. Research to identify more effective drugs for treating advanced disease continues.

Hepatotoxicity associated with cisplatin chemotherapy.

OBJECTIVE: To report a case of possible cisplatin-associated hepatotoxicity. CASE SUMMARY: A 69-year-old man received three cycles of cisplatin (100 mg/m2) and fluorouracil (1000 mg/m2/d for five days) for management of squamous cell carcinoma of the head and neck. Liver enzyme concentrations were within normal limits prior to each cycle of therapy but the aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase concentrations increased on the second day of each cycle. The concentrations began to decline on day 3 of each course, despite continued fluorouracil administration, and returned to normal by day 10. The patient's antiemetic therapy included metoclopramide in cycle 1 and ondansetron in cycles 2 and 3, which may have contributed to the enzyme elevations. DISCUSSION: Case reports of cisplatin-associated hepatotoxicity are reviewed. An association between cisplatin administration and hepatotoxicity is proposed in this patient. CONCLUSIONS: This patient may have experienced cisplatin-induced liver damage. Metoclopramide and ondansetron may have contributed to this effect.

Idarubicin: an anthracycline antineoplastic agent.

The mechanism of action, pharmacokinetics, activity, adverse effects, and administration of idarubicin are reviewed. Idarubicin is currently approved for use with other agents in the management of acute nonlymphocytic leukemia in adults. This drug is a structural analogue of daunorubicin and has the same mechanism of action as daunorubicin and doxorubicin. Unlike the other currently available anthracyclines, idarubicin has significant oral bioavailability (average 28%), and an oral dosage form is currently under investigation. Idarubicin is at least as effective as daunorubicin for acute nonlymphocytic leukemia, and two studies indicate greater activity and longer survival with an idarubicin-cytarabine regimen than with a daunorubicin-cytarabine regimen. Additional data indicate activity in acute lymphocytic leukemia, lymphomas, and breast cancer. Adverse effects are similar to those seen with other anthracyclines, although idarubicin may be associated with less cardiotoxicity than doxorubicin or daunorubicin. A maximum cumulative dose to prevent chronic cardiomyopathy has not yet been defined. Idarubicin is an effective agent for the management of acute nonlymphocytic leukemia and is reportedly more potent and less cardiotoxic than daunorubicin or doxorubicin.

Zidovudine and other reverse transcriptase inhibitors in the management of human immunodeficiency virus-related disease.

Licensed in 1987, zidovudine remains the only medication with proved efficacy for the treatment of disease caused by the human immunodeficiency virus (HIV). New information on the pharmacology (adults and children), effects of kidney and liver dysfunction on the disposition of the drug, and drug-drug interactions have improved the way we use and monitor this agent. The serious toxicity associated with zidovudine has led researchers to develop safer dosage regimens. Also, recognition that zidovudine slows but does not halt progression of disease has increased the search for effective alternatives. The best-studied agents are didanosine (2',3'-dideoxyinosine, ddl), zalcitabine (2',3'-dideoxycytidine, ddC), and foscarnet.

Acute hypotensive reaction to etoposide with successful rechallenge: case report and review of the literature.

Hypotension, bronchospasm, and facial flushing associated with an intravenous infusion of etoposide occurred in a 38-year-old man with advanced testicular cancer. The reaction began within three minutes after the initiation of the infusion and was reversed with intravenous fluids and diphenhydramine. He was successfully retreated with four additional doses of etoposide after pretreatment with diphenhydramine and dexamethasone. The literature concerning similar anaphylactoid reactions to intravenous etoposide is reviewed.

Acute cerebellar syndrome, conjunctivitis, and hearing loss associated with low-dose cytarabine administration.

An unusual reaction associated with chronic low-dose cytarabine is described. A 77-year-old man complained of three to four weeks of hearing loss and progressive inability to walk without assistance. He had received two courses of cytarabine 100 mg sc/wk for the management of myelofibrosis myeloid metaplasia over 21 months. He received a total of 3 g over seven months during his first course followed ten months later with a 1.2 g over four months. Conjunctivitis was also identified on physical examination at the time of his admission. He was admitted to the neurology service where a complete neurological work-up with consultations from the ophthalmology, audiology, hematology, and ear, nose, and throat services failed to identify a cause of his symptoms. Cytarabine was discontinued on the suspicion that his symptoms were drug induced. The conjunctivitis resolved completely with ophthalmic antibiotics and corticosteroids. His hearing slowly improved over three to four weeks, and he was able to ambulate with a walker. He continued to improve at home although some hearing loss remained three months after his initial presentation. Although conjunctivitis and neurotoxicity are well-known complications of high-dose cytarabine, there are no prior reports of these reactions after low-dose therapy. Hearing loss, which has not been previously reported with cytarabine alone, appears to be a new complication of cytarabine administration.

Hepatotoxicity associated with choline magnesium trisalicylate: case report and review of salicylate-induced hepatotoxicity.

A case of a 21-year-old woman who had developed mild hepatotoxicity while receiving choline magnesium trisalicylate therapy is described. She presented with fever and mild hepatic enzyme elevations before salicylate therapy was instituted. Liver function tests (LFT) returned to normal within five days of hospitalization but she continued to develop daily fevers. Blood, urine, and throat cultures were negative. An acute viral illness or reactivation of systemic lupus erythematosus were the suspected diagnoses. Choline magnesium trisalicylate was then administered in an effort to control her fever, and was successful. After three days of salicylate therapy her LFT values began to rise. They continued to rise for five more days before salicylate hepatotoxicity was suspected. Choline magnesium trisalicylate was discontinued after eight days and the patient's LFT quickly returned to normal. The source of fever was never identified, although infection with cytomegalovirus was considered the most likely cause. Salicylate-induced hepatotoxicity is reviewed.

Adrenal corticosteroids as antiemetics during cancer chemotherapy.

Adrenal corticosteroids were first reported in 1979 to have antiemetic effects during cancer chemotherapy. Since then considerable numbers of trials have been conducted to evaluate their activity alone and in combination with other agents. The majority of the research has centered on dexamethasone, although other corticosteroids have been studied. Dexamethasone as a single agent is superior to placebo and appears to be more effective than standard doses of prochlorperazine when administered with highly emetic agents. Dexamethasone is comparable to metoclopramide against moderately emetogenic agents and low-dose cisplatin, but less effective than metoclopramide against highly emetic agents or high-dose cisplatin. Dexamethasone improves the activity of prochlorperazine and metoclopramide and may reduce some of the side effects associated with the latter. Current trials continue to explore the role of corticosteroids alone and in combination with antiemetics.

Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue.

Epirubicin (4'-epidoxorubicin) is an antineoplastic agent derived from doxorubicin. The compounds differ in the configuration of the hydroxyl group at the 4' position. Epirubicin, like doxorubicin, exerts its antitumor effects by interference with the synthesis and function of DNA and is most active during the S phase of the cell cycle. Epirubicin is administered by intravenous (IV) injection. It is metabolized by the liver and primarily eliminated in the bile. About 10% of the drug is eliminated in the urine. Dosage adjustments are recommended for patients with liver metastases or elevated liver function tests. The elimination half-life of epirubicin is 30 to 40 hours. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, and pancreatic cancer. There is also evidence of activity against gastric cancer, small-cell lung cancer, and acute leukemia. Epirubicin has limited activity as a single agent against head and neck tumors or non-small-cell lung cancer, but may be beneficial in combination with other agents. The overall activity of epirubicin appears to be comparable with that of doxorubicin. However, more studies are needed to define its role in combination chemotherapeutic regimens. The acute dose-limiting toxicity of epirubicin is myelosuppression. Nausea, vomiting, and alopecia are also common. Epirubicin may cause transient cardiac arrhythmias and alterations of the electrocardiogram. Chronic therapy is limited, but available data indicate that epirubicin can be administered in higher cumulative doses than doxorubicin before cardiotoxicity limits further therapy.

Bleomycin pneumonitis potentiated by oxygen administration.

A case of a 53-year-old man who developed acute pneumonitis after bleomycin and moderate oxygen administration is presented. The patient received bleomycin 189 U over five days for preoperative control of a squamous cell carcinoma of the right tongue and tonsil. Surgery to remove the remaining tumor was performed 19 days later. The highest intraoperative oxygen concentration was 33 percent, but 40 percent oxygen was administered for four days postoperatively. He became febrile and developed a productive cough and pulmonary infiltrates on postoperative day 4. Despite antibiotic therapy, his pulmonary function deteriorated and 100 percent oxygen was required to maintain adequate oxygenation. He sustained a myocardial infarction on postoperative day 7 and progressively deteriorated and expired five days later. Autopsy findings were consistent with bleomycin and oxygen-induced pulmonary damage. Oxygen potentiation of bleomycin-induced pulmonary toxicity is discussed.