There was no evidence of a general cognitive decline or progression of white matter changes after 3 years. Results argue for limited damage from XRT at this frequently used dose and volume in the absence of other clinical risk factors.

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A prospective study of patients receiving cis-diaminedichloroplatin I1 (DDP) was carried out to determine if risk factors could be identified related to the patient's living habits or past medical history that would predict in which patients DDP neuropathy might develop. Sixty-nine patients receiving six different combinations of chemotherapeutic agents, including DDP were examined. Twenty-eight of these patients received DDP in combination with the radioprotective agent S-2-(3-aminopropylamino)-ethylphosporothioic acid (WR 2721). No risk factors were identified relating to personal habits or past medical history of the patients. However, patients receiving DDP (40 mg/m2) on 5 consecutive days had a significantly higher incidence of neuropathy. Patients receiving DDP in combination with WR 2721 had a significantly lower incidence of neuropathy, and the mean dose at onset was significantly higher than the mean dose at onset of neuropathy for all other groups. In addition, five of six patients who were available for long-term follow-up demonstrated nearly complete reversal of the signs and symptoms of neuropathy.Cancer 61:2192-2195,1988.HE NEUROPATHY ASSOCIATED WITH cis-diamine-The character of the neuropathy is remarkably uniform in the literature and is replacing the nephropathy as the dose-limiting toxicity. 1-5 Patients usually complain of numbness or tingling as the first symptom, and examination initially shows decreased vibratory sensation and decreased or absent deep tendon reflexes. As the neuropathy continues, position sense also is impaired, and a marked sensory ataxia develops in severely affected patients.Although the neuropathy is generally dose-dependent, we had noticed a wide variation in the severity of symptoms among patients at equivalent doses. This prompted us to do a prospective study of patients receiving DDP at the Hospital of the University of Pennsylvania to see if we could identify risk factors that would predict in which patients neuropathy would develop and how severely they might be affected.We found that the schedule of administration is one important factor in determining the incidence of neuFrom the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.Supported in part by the NIH (NS00563, NS08075, NS00865), the Muscular Dystrophy Association of America, and the Bnstol-Meyers Company.The authors thank the National Cancer Institute for supplying the WR 2721.Address for reprints: Joan E. Mollman, MD, Department of Neurology, 3400 Spruce Street, Philadelphia, PA 19104.Accepted for publication November 13, 1987. ropathy. We also found that S-2-(3-aminopropylamino)-ethylphosporothioic acid (WR 272 l), a radioprotective compound, partially protects peripheral nerves from DDP toxicity. In addition, we have been able to observe five patients long enough to see partial or complete resolution of symptoms. Patients and MethodsPatients receiving DDP were evaluated by a single neurologist before beginning therapy and periodically throughout their course. Sixty-eight of 69 p...

Primary CNS malignancies are responsible for approximately 12,000 deaths annually in the United States. There has been little change in the outcome for adults with malignant brain tumors over the past few decades, despite improvements in surgical techniques and advances in radiation therapy. These tumors are uniformly fatal one to two years after diagnosis. The morbidity and mortality of this disease arise from the effects of a locally invasive, non-metastasizing lesion. The patients may suffer from seizures, paralysis, incoordination, aphasia, confusion, memory loss, sensory deficits or visual loss, depending on the regions of the brain affected. In addition, they usually require large doses of corticosteroids early and late in their illness, and may experience disabling side effects of this treatment, such as edema, proximal myopathy, diabetes, fungal infections or deep vein thrombosis. Few patients in the older age group are able to work after the diagnosis. Most of the patients are incapable of self-care for several months before death. The localized transfer of new genes into cancer cells potentially permits the expression of proteins with specific biologic functions that may provide a means to alter the biology of tumor growth through a variety of mechanisms including increasing tumor immunogenicity, inducing the local expression of toxic agents, and sensitization of tumors to chemotherapeutic agents. Gene therapy with the transfer of the drug susceptibility gene Herpes virus thymidine kinase (HSV-TK) has shown promise in a number of animal models, including CNS tumors. This study will evaluate the use of adenovirus-mediated transfer of the HSV-TK gene into primary human brain tumors followed by systemic treatment with ganciclovir. The goals of this phase I study are to evaluate the overall safety and efficacy of this treatment and to gain insight into the parameters that may limit the general applicability of this approach. In this phase I study, patients with recurrent gliomas will receive stereotactic-guided injections of the virus into the brain tumor, followed by intravenous ganciclovir for 14 days. Patients eligible to undergo a palliative debulking procedure will receive the same treatment followed by resection on day 7. At the time of resection a second dose of virus will be administered intra-operatively into the residual, unresectable portion of the tumor, and intravenous ganciclovir will be continued for additional 14 days. Tissue removed at the time of resection will be analyzed for evidence of adenovirus infection, thymidine kinase expression and signs of inflammation. The size and metabolic activity of all tumors will be followed by volumetric MRI scans and Position Emission Tomography Scans, respectively. Patients will be enrolled in groups of three, with each group receiving successively larger doses of adenovirus. This study will quantify the toxicity of this therapy, and provide evidence as to the duration of transgene expression and virus induced inflammation.