Two-Year Tumor Outcomes of a Phase 2B, Randomized, Double-Blind Trial of Avasopasem Manganese (GC4419) Versus Placebo to Reduce Severe Oral Mucositis Owing to Concurrent Radiation Therapy and Cisplatin for Head and Neck Cancer.

PURPOSE: Avasopasem manganese (GC4419), an investigational selective dismutase mimetic radioprotector, reduced duration, incidence, and severity of severe oral mucositis (World Health Organization grade 3-4) in a phase 2b, randomized, double-blind trial of patients receiving concurrent cisplatin (cis) and radiation therapy (RT) for head and neck cancer. We report the secondary endpoints of final 1- and 2-year tumor outcomes and exploratory data on trismus and xerostomia. METHODS AND MATERIALS: Patients with locally advanced oral cavity or oropharynx cancer to be treated with definitive or postop cis and RT were randomized to 1 of 3 arms: 30 mg avasopasem, 90 mg avasopasem, or placebo. Pairwise comparisons of Kaplan-Meier estimates (each active arm separately vs placebo) were made for overall survival, progression-free survival, locoregional control, and distant metastasis-free survival. Xerostomia and trismus data were collected at each follow-up visit and analyzed for trends by post-RT timepoint and treatment group. RESULTS: At a median follow-up for the entire cohort of 25.5 months (25th-75th percentile, 24.6-26.2 months; range, 0.2-31.9 months), Kaplan-Meier estimates of 1- and 2-year overall survival, progression-free survival, locoregional control, and distant metastasis-free survival were not statistically different. No trends were apparent in xerostomia or trismus data. CONCLUSIONS: Avasopasem does not lead to statistically different tumor control outcomes when used concurrently with cis and RT for head and neck cancer. There was no detectable effect on trismus or xerostomia.

Solitary Leptomeningeal Recurrence From Prostate Adenocarcinoma After Treatment With Cytotoxic Gene Therapy, Radiation Therapy, and Androgen Deprivation Therapy.

PURPOSE: Leptomeningeal disease in prostate adenocarcinoma is very rare. Solitary leptomeningeal recurrence from prostate adenocarcinoma has only been previously reported once in the published literature. METHODS AND MATERIALS: A 63-year-old man with high-risk prostate cancer was treated in a phase I-II trial with androgen deprivation, radiation therapy, and cytotoxic gene therapy. He initially had biochemical control but experienced solitary leptomeningeal recurrence 47 months after diagnosis. RESULTS: He received androgen deprivation, radiation therapy to the lumbar and sacral spine, and stereotactic radiosurgery to 3 intracranial foci of disease. He died 14 months after leptomeningeal recurrence. Autopsy showed diffuse spinal leptomeningeal disease, leptomeningeal based intracranial lesions, and no other metastasis. CONCLUSIONS: The cause for solitary leptomeningeal recurrence in this patient is unknown. Although there may be many possible mechanisms, we speculate that it could be related to his initial treatment with cytotoxic gene therapy along with radiation therapy and androgen deprivation.

Local control after intensity-modulated radiotherapy for head-and-neck rhabdomyosarcoma.

PURPOSE: To examine the patterns of failure in patients treated with intensity-modulated radiotherapy (IMRT) for head-and-neck rhabdomyosarcoma (RMS). METHODS AND MATERIALS: Between 1998 and 2005, 19 patients with a diagnosis of head-and-neck RMS received IMRT at The Methodist Hospital. There were 11 male and 8 female patients, with a median age of 6 years at time of irradiation. Tumor location was parameningeal in 7, orbital in 6, and other head-and-neck RMS in 6. Chemotherapy was given to all patients, with vincristine, actinomycin D, and cyclophosphamide being the most common regimen (n = 18). The median prescribed dose was 5040 cGy. The clinical target volume included the gross tumor volume with a 1.5-cm margin. The median duration of follow-up for surviving patients was 56 months. RESULTS: The 4-year overall survival and local control rates were 76% and 92.9%, respectively. One patient developed a local failure in the high-dose region of the radiation field; there were no marginal failures. Distant metastasis was seen in 4 patients. Overall survival was 42.9% for parameningeal sites and 100% for other sites (p < 0.01). Late toxicities were seen in 7 patients. Two secondary malignancies occurred in 1 child with embryonal RMS of the face and a p53 mutation. CONCLUSIONS: Local control was excellent in patients receiving IMRT for head-and-neck RMS. Patterns of local failure reveal no marginal failures in this group of patients.