valacyclovir and Brain-Neoplasms

Despite aggressive standard of care (SOC) treatment, survival of malignant gliomas remains very poor. This Phase II, prospective, matched controlled, multicenter trial was conducted to assess the safety and efficacy of aglatimagene besadenovec (AdV-tk) plus valacyclovir (gene-mediated cytotoxic immunotherapy [GMCI]) in combination with SOC for newly diagnosed malignant glioma patients.. Treatment cohort patients received SOC + GMCI and were enrolled at 4 institutions from 2006 to 2010. The preplanned, matched-control cohort included all concurrent patients meeting protocol criteria and SOC at a fifth institution. AdV-tk was administered at surgery followed by SOC radiation and temozolomide. Subset analyses were preplanned, based on prognostic factors: pathological diagnosis (glioblastoma vs others) and extent of resection.. Forty-eight patients completed SOC + GMCI, and 134 met control cohort criteria. Median overall survival (OS) was 17.1 months for GMCI + SOC versus 13.5 months for SOC alone (P = .0417). Survival at 1, 2, and 3 years was 67%, 35%, and 19% versus 57%, 22%, and 8%, respectively. The greatest benefit was observed in gross total resection patients: median OS of 25 versus 16.9 months (P = .0492); 1, 2, and 3-year survival of 90%, 53%, and 32% versus 64%, 28% and 6%, respectively. There were no dose-limiting toxicities; fever, fatigue, and headache were the most common GMCI-related symptoms.. GMCI can be safely combined with SOC in newly diagnosed malignant gliomas. Survival outcomes were most notably improved in patients with minimal residual disease after gross total resection. These data should help guide future immunotherapy studies and strongly support further evaluation of GMCI for malignant gliomas.. ClinicalTrials.gov NCT00589875.

Topics: Acyclovir; Adenoviridae; Adult; Aged; Antiviral Agents; Brain Neoplasms; Chemotherapy, Adjuvant; Genetic Therapy; Genetic Vectors; Glioma; Humans; Immunotherapy; Middle Aged; Simplexvirus; Survival Analysis; Thymidine Kinase; Treatment Outcome; Valacyclovir; Valine

Despite aggressive therapies, median survival for malignant gliomas is less than 15 months. Patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) fare worse, presumably because of temozolomide resistance. AdV-tk, an adenoviral vector containing the herpes simplex virus thymidine kinase gene, plus prodrug synergizes with surgery and chemoradiotherapy, kills tumor cells, has not shown MGMT dependency, and elicits an antitumor vaccine effect.. Patients with newly diagnosed malignant glioma received AdV-tk at 3 × 10(10), 1 × 10(11), or 3 × 10(11) vector particles (vp) via tumor bed injection at time of surgery followed by 14 days of valacyclovir. Radiation was initiated within 9 days after AdV-tk injection to overlap with AdV-tk activity. Temozolomide was administered after completing valacyclovir treatment.. Accrual began December 2005 and was completed in 13 months. Thirteen patients were enrolled and 12 completed therapy, three at dose levels 1 and 2 and six at dose level 3. There were no dose-limiting or significant added toxicities. One patient withdrew before completing prodrug because of an unrelated surgical complication. Survival at 2 years was 33% and at 3 years was 25%. Patient-reported quality of life assessed with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) was stable or improved after treatment. A significant CD3(+) T-cell infiltrate was found in four of four tumors analyzed after treatment. Three patients with MGMT unmethylated glioblastoma multiforme survived 6.5, 8.7, and 46.4 months.. AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas. Temozolomide did not prevent immune responses. Although not powered for efficacy, the survival and MGMT independence trends are encouraging. A phase II trial is ongoing.

Topics: Acyclovir; Adenoviridae; Adjuvants, Immunologic; Adult; Aged; Antineoplastic Agents, Alkylating; Antiviral Agents; Brain Neoplasms; Cancer Vaccines; Combined Modality Therapy; Dacarbazine; Genetic Therapy; Genetic Vectors; Glioma; Herpesvirus 1, Human; Humans; Immunotherapy; Middle Aged; O(6)-Methylguanine-DNA Methyltransferase; Temozolomide; Thymidine Kinase; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Aged; Antiviral Agents; Brain Neoplasms; Diagnosis, Differential; Encephalitis, Varicella Zoster; Glioma; Gliosis; Humans; Immunocompetence; Magnetic Resonance Imaging; Male; Middle Aged; Valacyclovir; Valine; Young Adult

We report a case of a 73-year-old patient with complete ophthalmoplegia following an episode of ophthalmic herpes zoster. MRI showed an associated ipsilateral temporal meningioma with cavernous sinus extension. We discuss the possible responsibility of these two conditions in the ocular motor signs.

Topics: Acyclovir; Aged; Anisocoria; Anti-Inflammatory Agents; Antiviral Agents; Blepharoptosis; Brain Neoplasms; Female; Herpes Zoster Ophthalmicus; Humans; Magnetic Resonance Imaging; Meningioma; Methylprednisolone; Ophthalmoplegia; Temporal Lobe; Valacyclovir; Valine; Visual Acuity