A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression.

A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim. Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of i.v. antibiotic therapy compared with patients who received filgrastim. Both growth factors were well tolerated. No patient was readmitted to the hospital after growth factor was discontinued. Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.

Randomized trial comparing the tolerability of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in cancer patients receiving myelosuppressive chemotherapy.

A prospective, randomized, double-blind, multicenter study in cancer patients receiving myelosuppressive chemotherapy was undertaken to evaluate and compare the tolerability of sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the prophylaxis or treatment of chemotherapy-induced neutropenia. In all, 137 evaluable patients received sargramostim (300 micrograms; 193 mg/m2) or filgrastim (481 mg; 7 mg/kg) once daily by self-administered s.c. injection, usually beginning within 48 h after completion of chemotherapy. With the exception of a slightly higher incidence of grade 1 fever (< 38.1 degrees C) with sargramostim, there were no statistically significant differences in the incidence or severity of local or systemic adverse events possibly related to the growth factors. Although the study was not designed to evaluate efficacy directly, there also were no statistically significant differences between treatment groups in total days of growth factor therapy, days of hospitalization, or days of i.v. antibiotic therapy during the treatment period. Both sargramostim and filgrastim were comparably well tolerated when given by s.c. injection in this group of patients, and no clinically significant differences between the growth factors were demonstrated.

Outbreak of Pseudomonas cepacia bacteremia in oncology patients.

In 1991, an outbreak of Pseudomonas cepacia bacteremia (PCB) occurred among patients at an oncology clinic in Alabama. A case-patient was defined as any patient at Alabama Oncology Hematology Associates (AOHA) who had at least one blood culture positive for P. cepacia from 7 August through 31 October. Fourteen case-patients were identified; all required hospitalization (median duration, 17 days), but none died of PCB. A cohort study assessing risk factors for PCB focused on all patients who had been treated on the 8 days when case-patients had last visited AOHA during the period 7-21 August. Only patients with central venous catheters developed PCB (P < .001). Among patients with central venous catheters, PCB occurred only after visits to AOHA at which the catheters were flushed with heparin solution in the AOHA laboratory rather than in the treatment area (P < .001). P. cepacia was cultured from the only intravenous fluid bag used to prepare heparin flush solution in the laboratory during the interval 7-21 August. All outbreak-associated isolates of P. cepacia had an identical DNA ribotype pattern. These findings emphasize the importance of avoiding multiple use of single-use solutions, especially for high-risk patients with long-term indwelling central venous catheters.

Inflammatory fibrous histiocytoma: an important variant of malignant fibrous histiocytoma highly responsive to chemotherapy.

Inflammatory fibrous histiocytoma is a recently recognized variant of malignant fibrous histiocytoma. Patients managed with surgical excision or radiation therapy usually have had multiple recurrences, often with metastases. The disease is insidious but ultimately fatal. Four consecutive patients were treated with inflammatory fibrous histiocytoma with alkylating agents with or without anthracyclines and produced prolonged and sustained remissions. Inflammatory fibrous histiocytoma may be another highly chemotherapeutically responsive tumor that deserves active case identification for aggressive curative therapy.

Bone marrow necrosis and degeneration.

Bone marrow necrosis, regarded as a rare finding in specimens from living patients, has been associated with a poor prognosis in patients with serious hematologic diseases and metastatic carcinoma. Two patients with extensive idiopathic bone marrow necrosis and a relatively benign course of illness were found. Therefore, we examined 500 consecutive bone marrow biopsy specimens that were obtained in a university hospital complex. Review of this material showed evidence of necrosis and degenerative changes of variable severity in one third of the biopsy specimens. It was found with approximately the same incidence in patients who underwent bone marrow biopsy for either neoplastic or nonneoplastic disorders; an increased prevalence was not observed in the group of patients who had received chemotherapy. Based on these observations, we believe necrosis and degeneration of the bone marrow is a commonplace finding that is frequently overlooked in a wide variety of acute and chronic disorders, and that requires further investigation to determine its clinical importance.

Unusual manifestations of non-Hodgkin's lymphoma.

Two patients with biopsy proven lymphomatous infiltration of uncommon sites are presented. One had histiocytic lymphoma, involving the true vocal cord with a squamous cell carcinoma on the opposite vocal cord. The other had diffuse well-differentiated lymphocytic lymphoma, presenting with nodal and periorbital disease. After local radiation therapy and while clinically free of other lesions, he developed hemotochezia due to several polypoid lesions throughout the entire colon and prostatic infiltration with symptoms of lower urinary tract obstruction. Both problems were solved after specific treatment.

Pulmonary toxicity associated with bischloroethylnitrosourea (BCNU).

Ten patients developed pulmonary fibrosis after bischloroethylnitrosourea (BCNU) therapy for malignancy. This was lethal in seven patients, four of whom had no evidence of tumor at autopsy. Presenting symptoms were either the insidious onset of cough and dyspnea or the sudden onset of respiratory failure. Physical findings were unremarkable. Chest roentgenogram usually showed interstitial infiltrates. Pulmonary function studies showed resting hypoxia with diffusion and restrictive defects. This complication of therapy does not appear to be dose related and may be made more likely by the concomitant administration of cyclophosphamide. Prednisone therapy did not benefit most patients. The literature and the implications of the use of BCNU alone or in combination are reviewed.

Combination chemotherapy with CCNU (NSC-79037),hexamethylmelamine (NSC-13875) and methotrexate (NSC-740) in advanced bronchogenic carcinoma.

18 patients with metastatic or recurrent bronchogenic carcinoma and one patient with a squamous cell carcinoma of the trachea were treated with a combination of CCNU, hexamethylmelamine and methotrexate. Objective remissions were observed in 3/19 (16%): 1 complete, 1 partial (greater than 50%) and 1 incomplete (less than 50%). However, the patient with the complete response was the only drug death, on day 21. Remission duration in the other two patients was 3 and 9+ months respectively. One patient with oat cell carcinoma experienced no tumor progression for 5 months. This combination resulted in severe gastrointestinal toxicity in 5/19, severe thrombopenia in 12/19 and severe neutropenia in 6/19. We conclude that the combination as used here resulted in no increased clinical effectiveness and proved to be quite toxic.