imuvert and Astrocytoma

Malignant astrocytoma is a fatal, primary brain tumor affecting adults in the prime of life. Even with optimal treatment, median life expectancy from time of diagnosis is 51 weeks. Standard therapy consists of surgical debulking, radiation therapy and chemotherapy. Immunotherapy, utilizing biologic response modifiers (BRMs), affords one of the more promising treatment modalities. ImuVert, a BRM derived from Serratia marcescens, was recently granted orphan drug status by the Food and Drug Administration. In phase I and II clinical trials in patients with advanced malignant tumors, toxicities ranged from mild local reaction at injection sites to hypotension requiring vasopressors. ImuVert is currently being tested in a multicenter clinical trial as a treatment for recurrent malignant astrocytoma in adult patients. A comprehensive toxicity profile of brain tumor patients receiving ImuVert and techniques of managing adverse effects is presented.

Topics: Antineoplastic Agents; Astrocytoma; Biological Products; Brain Neoplasms; Humans; Immunologic Factors; Neoplasm Recurrence, Local

A clinical trial was undertaken to determine the safety and efficacy of combining a biologic response modifier derived from the bacterium Serratia marcescens (ImuVert) and radiation therapy (RT) in patients with newly diagnosed anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM).. Fifteen patients who had undergone either a gross total resection, a partial resection, or a biopsy were treated concurrently with ImuVert and RT. Safety and tolerance were examined by assessment of symptomatic reactions recorded at each ImuVert treatment. Efficacy of treatment was examined in terms of time to progression of tumor and survival.. All patients experienced local reactions at the injection sites that consisted of erythema and induration. The majority of patients experienced flu-like symptoms. Hypotension was responsible for the most significant morbidity (which required fluid resuscitation and extended observation) and dose deescalation. No patients were removed from the study because of toxicity. There were no on-study deaths related to ImuVert treatment. Median time to progression was 33.4 weeks, and median survival was 78 weeks.. These results compare favorably with those of recent studies in patients with malignant astrocytomas who received multimodality therapy.

Topics: Adult; Aged; Astrocytoma; Biological Products; Brain Neoplasms; Combined Modality Therapy; Female; Glioblastoma; Humans; Immunologic Factors; Male; Middle Aged; Serratia marcescens; Survival Analysis

Nineteen assessable patients with recurrent malignant astrocytomas who had failed standard therapy (surgery, radiation, and/or chemotherapy) were treated on a phase I-II trial with a biologic extract of Serratia marcescens (ImuVert; Cell Technology, Boulder, CO) a new biologic response modifier (BRM). Two complete responses (CRs) were seen, of 63 and 77+ weeks duration. One minor response (MR) occurred, of 6 weeks duration. There were four additional stable (S) patients, with durations of 58+, 39, 12, and 7 weeks. Median time to progression and median survival in the CR plus MR patients were 63 and 129+ weeks, respectively. Overall, median time to progression and median survival were 12 and 19 weeks, respectively. Three patients are alive greater than or equal to 2.5 years from study entry. Common toxicities included transient (less than 72 hours) tenderness, induration, and erythema at the injection sites. Systemic toxicities were less frequent and included fever, chills, nausea/vomiting, headache, arthralgia, and hypotension. The response rate (CR plus MR) to this new BRM is modest (16%). However, the observation of CRs in patients with advanced recurrent malignant astrocytomas, with acceptable overall toxicity, warrants further study of this agent.

Topics: Adult; Aged; Antineoplastic Agents; Astrocytoma; Biological Products; Brain Neoplasms; Drug Evaluation; Female; Fever; Humans; Immunologic Factors; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Remission Induction; Serratia marcescens; Survival Rate; Vomiting