trimethoprim--sulfamethoxazole-drug-combination and Glioblastoma

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antineoplastic Agents, Alkylating; Brain Neoplasms; Diabetes Insipidus, Nephrogenic; Glioblastoma; Humans; Hydrochlorothiazide; Kidney Function Tests; Male; Middle Aged; Nephritis, Interstitial; Sodium Chloride Symporter Inhibitors; Temozolomide; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

This report presents the case of a 67-year-old woman affected by glioblastoma. After a few days of adjuvant therapy with temozolomide and prophylaxis with trimetrophin-sulfamethoxazolo to prevent Pneumocystis Jiroveci, she had progressive and rapid worsening of symptoms with weakness, dyspnea and orthopnea. She had peripheral edema and proximal hyposthenia of the lower limbs. Chest CT showed bilateral ground-glass opacities and laboratory exams revealed hypoxemia and hypocapnia, an initial reduction in platelet and white blood cells, and an elevation of LDH, AST, ALT, and active urinary sediment. Blood cultures, bronchoalveolar lavage (BAL) data and transbronchial biopsy showed no infections, and in particular no evidence of Pneumocystis Jiroveci pneumonia. Histological examination revealed a typical pattern of AIP. She was treated with broad-spectrum antibiotics and high-dose steroids. The symptoms worsened and respiratory failure required mechanical ventilation. The pneumonia was not responsive to medical or invasive care. She died after ten days of hospitalization. At present very little can be found in the literature about lung toxicity caused by temozolomide. This case can be added as a new report describing this risk. The combination therapy with temozolamide and trimetophin-sulfamethoxazolo could have a synergistic action inducing various forms of pulmonary toxicity. ESTABLISHED FACTS: Acute interstitial pneumonia is a common manifestation of lung toxicity caused by drugs. The clinical course is favorable with a good response to corticosteroids. NOVEL INSIGHT: This is the first fatal case of lung toxicity caused by Temozolomide. Clinicians must be aware that a combination therapy including trimetophin-sulfamethoxazolo could have a synergistic action in inducing pulmonary toxicity.

Topics: Aged; Antineoplastic Agents, Alkylating; Blood Gas Analysis; Brain Neoplasms; Bronchoalveolar Lavage Fluid; Dacarbazine; Electrocardiography; Fatal Outcome; Female; Glioblastoma; Humans; Lung; Lung Diseases, Interstitial; Physical Examination; Pneumocystis carinii; Pneumonia, Pneumocystis; Temozolomide; Trimethoprim, Sulfamethoxazole Drug Combination

Temozolomide (TMZ) is a cytotoxic agent of the imidazotetrazine class, chemically related to dacarbazine. Its use poses higher risks of lymphopenia and opportunistic infections. Prophylaxis for Pneumocystis jiroveci must be considered up to 12 months after treatment discontinuation. The due literature (MEDLINE) makes no mention of a possible connection between the use of TMZ and tuberculosis (TB). A female patient, aged 59, featuring glioblastoma multiforme and having undergone solely a brain biopsy, was submitted to TMZ along with radiotherapy. After the first TMZ maintenance cycle, the referred patient was admitted displaying a background of a 40-day afternoon fever and productive coughing. She was thus submitted to a bronchoscopy and LBA, which resulted BAAR 1+/4+. TMZ was then suspended, and rifampicin, isoniazid, and pyrazinamide introduced. Considerations on prophylaxis with isoniazide in cancer patients are long-lived and scarce. Some subgroups are likely to benefit from the prophylactic administration of isoniazide during TMZ treatment, such as those patients under high doses of corticoids, patients with past medical history of TB, the malnourished, patients from endemic regions, and patients with highly reactive tuberculinic tests. That, nevertheless, must not restrict the administration of TMZ, but, rather, stand for a warning about its possible toxicity, and thus mitigate complications.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Ulcer Agents; Antibiotics, Antitubercular; Anticholesteremic Agents; Anticonvulsants; Antineoplastic Agents, Alkylating; Atorvastatin; Brain Neoplasms; Combined Modality Therapy; Cyclosporine; Dacarbazine; Dexamethasone; Female; Fluoxetine; Glioblastoma; Heptanoic Acids; Humans; Immunosuppressive Agents; Isoniazid; Middle Aged; Omeprazole; Phenobarbital; Prednisone; Pyrazinamide; Pyrroles; Radiotherapy; Red-Cell Aplasia, Pure; Rifampin; Temozolomide; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

A review was undertaken of the clinical features and results of diagnostic tests in non-HIV infected patients who developed granulomatous Pneumocystis carinii pneumonia (PCP).. A retrospective review was performed of the charts and radiographs of patients with a granulomatous reaction to P carinii identified from computerised pathology records at Memorial Sloan Kettering Cancer Center, a university affiliated tertiary care hospital.. Three cases were identified; the incidence of granulomatous PCP was 3%. All patients had risk factors for PCP and had received high dose corticosteroids which had been stopped. Two patients had received chemotherapy. Presentation was insidious with only mild symptoms; only one patient had fever. Chest radiographs showed a reticulonodular pattern. Bronchoscopy was negative for PCP in all cases and open lung biopsy was necessary.. A granulomatous pathological reaction to PCP occurs rarely in patients with malignancy. In these cases the clinical presentation may be atypical and bronchoscopy can be non-diagnostic.

Topics: Adolescent; Adult; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Female; Glioblastoma; Granuloma; Hodgkin Disease; Humans; Male; Middle Aged; Pneumocystis Infections; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination