The role of chemotherapy in the treatment of gliomas in adults

Abstract

Glioblastomas and previously irradiated recurrent gliomas remain incurable. Chemotherapy is able to palliate patients by shrinking tumors, thereby improving neurological status and quality of life. Chemotherapy may also be capable of prolonging survival in some instances. The effectiveness of chemotherapy against gliomas is comparable to the efficacy of chemotherapy against many other solid tumors. When given in an adjuvant setting along with radiation postoperatively, studies suggest that the nitrosoureas, dibromodulcitol, dianhydrogalactitol, procarbazine, teniposide, dacarbazine, and cisplatin may possibly be useful, although results for many of these drugs are inconclusive. Some chemotherapy combinations also appear to be useful in an adjuvant setting, particularly BCNU plus ifosfamide, BCNU plus cisplatin, CCNU plus dibromodulcitol, and CCNU plus lonidamine. However, there is not yet conclusive evidence that combination chemotherapy is superior to single agent adjuvant chemotherapy in the treatment of gliomas. While the use of chemotherapy prior to postoperative cranial radiation is worthy of further study, it has not to date proven to be more effective than chemotherapy combined with radiation. In patients whose tumors have recurred following radiation, palliation may be achieved with the nitrosoureas, procarbazine, teniposide, and diaziquone. Cisplatin, high dose methotrexate, the interferons, and a variety of other medications also may be of use. As in the case of adjuvant chemotherapy, chemotherapy combinations for recurrent tumor have not been conclusively demonstrated to be superior to single agent treatment, although some CCNU-based combinations are of interest. Many different chemotherapy drugs have been administered by intracarotid infusion. There is a moderately high risk of serious local retinal and neurological toxicity using this approach, and efficacy has not been proven to be improved by this approach. However, further studies of intraarterial administration of chemotherapy are warranted in light of theoretical considerations, pharmacological observations of enhanced local drug concentrations, and the observation that patients who.have failed the same drugs intravenously may respond when lower doses of the drug are administered intraarterially. In addition, some patients have had tumor shrinkage in the area infused while tumor has grown in other areas. Thus, while intracarotid chemotherapy must be regarded as still investigational and potentially quite toxic, further studies are indicated. High dose chemotherapy has been administered in combination with autologous bone marrow rescue. High response rates and prolonged survival durations have been reported in some instances, justifying further study despite substantial toxicity. Rapid intracarotid infusion of mannitol may transiently disrupt the blood-brain barrier. It remains controversial whether this substantially increases tumor concentrations of chemotherapeutic agents, and studies continue. There has been relatively little work done with intratumoral or intraventricular injections of chemotherapy for treatment of adult gliomas. There are theoretical reasons why neither treatment modality would be expected to be advantageous, but further limited studies continue. In summary, the use of chemotherapy in the treatment of gliomas in adults is being actively investigated. It can be anticipated that progress will be made in the years ahead.