Radiotherapy-induced Toxicity Research Articles

Nasopharyngeal carcinoma in childhood and adolescence: Analysis of a series of 32 patients treated with combined chemotherapy and radiotherapy

Standard therapy for nasopharyngeal carcinoma (NPC) in children has generally followed the guidelines established for adults. We report here, the treatment outcomes in 32 children and adolescents with NPC and we discuss treatment approaches. Between 1993 and 1997, 32 NPC patients aged ⩽20 years (mean age 15 years) were treated in our institution; they represented 18% of all NPC cases seen during the same time period. 27 patients had no metastases at diagnosis; 26 of these were treated with primary chemotherapy combining epirubicin and cisplatin. Radiotherapy was then delivered to 22 patients at a mean dose of 70 Gy, either conventionally (6 patients) or bifractionated (16 patients). 5 patients had metastases at diagnosis and were treated with chemotherapy combining epirubicin, bleomycin and cisplatin before definitive radiotherapy. The objective response rate (OR) after chemotherapy was 90.9% at the primary site, with a 13.6% complete response (CR) rate. At nodal sites, the OR was 95.5% and the CR was 31.8%. Local control was obtained in all patients after definitive radiotherapy with a medium follow-up of 43.7 months. Late toxicity affecting quality of life was found in 26% of the children who were irradiated, especially among those under 15 years of age (skin fibrosis, 27%; trismus, 27%; hypothyroidism, 14%). No locoregional relapses were observed. Distant metastases occurred in 33% of cases, with a median delay of 4.7 months from the end of treatment. The 2- and 5-year overall survival (OS) rates were 76 and 56%, respectively. Disease-free survival (DFS) was 65% at 2 and 5 years. Therapeutic outcomes for childhood NPC were similar to those in adults, but with more radiotherapy-induced toxicity. New chemotherapeutic combinations and new radiotherapeutic techniques should be sought to improve both survival and quality of life.

The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects.

Radio- and chemotherapy for the treatment of malignancies are often associated with significant toxicity. One approach to reduce the toxicity is the concomitant treatment with chemoprotective agents. This article reviews two sulfhydryl compounds, namely the agent WR-2721 (amifostine), a compound recently registered for use in human in many countries, and the natural occurring compound glutathione (GSH). GSH is not registered as a chemoprotective agent. WR-2721 is an aminothiol prodrug and has to be converted to the active compound WR-1065 by membrane-bound alkaline phosphatase. WR-1065 and GSH both act as naturally occurring thiols. No protective effect on the tumour has been found when these compounds are administered intravenously. There is even in vitro evidence for an increased anti-tumour effect with mafosfamide after pretreatment with WR-2721, and in vivo after treatment with carboplatin and paclitaxel. Randomized clinical studies have shown that WR-2721 and GSH decrease cisplatin-induced nephrotoxicity and that WR-2721 reduces radiation radiotherapy-induced toxicity. Side-effects associated with WR-2721 are nausea, vomiting and hypotension, GSH has no side-effects. An exact role of WR-2721 and GSH as chemoprotectors is not yet completely clear. Future studies should examine the protective effect of these drugs on mucositis, cardiac toxicity, neuro- and ototoxicity, the development of secondary neoplasms and their effect on quality of life. © 1999 Cancer Research Campaign

Clinical and preclinical modulation of chemotherapy-induced toxicity in patients with cancer.

Anticancer treatment is generally associated with toxicity to health issues. One of the reasons for this unpleasant association is that anticancer agents have been mostly selected on the basis of an empirically established toxicity towards cancer cell lines and rapidly growing tumours in animal models, and not on the basis of a sophisticated intervention in tumour-specific biology. This strategy of drug development unavoidably produces drugs with toxicity towards normal cells and tissues which also have a high cell turnover and share many characteristics with tumour cells. Therefore it is a continuing challenge to design therapy which is both effective and also has high specificity for the biology of cancer and/or is efficiently targeted to tumour tissue. This article describes the mechanisms of cytotoxicity of standard chemo- and radiotherapy and discussed the possibilities of currently available cytoprotective agents to reduce or prevent these toxicities. These agents should ideally be selective for normal cells versus cancer cells, be effective in reducing or preventing toxicity, have no negative impact on anticancer therapy and have minimal adverse effects. None of the agents described in this article fulfils these criteria completely and therefore we cannot recommend these agents for standard use in daily anticancer practice. Nevertheless, there are encouraging data concerning the beneficial effects of dexrazoxane for anthracycline-induced cardiomyopathy and amifostine for platinum- and radiotherapy-induced toxicity. These date warrant further studies.

Definitive radiotherapy of prostatic cancer: The Norwegian radium hospital's experience (1976‐1982)

During the years 1976 to 1982 definitive curatively aimed radiotherapy to the primary tumor was given to 53 patients with prostatic cancer confined to the true pelvis (T0, 2; T1-2, 19; T3, 24; T4, 8; N0, 18; N+, 2; Nx, 33); all patients were of the Mo-category. The pelvic lymph nodes received a total dose of 2 Gy X 25 by means of an anterior and posterior radiation field. The prostatic gland was irradiated by an additional booster dose of 2 Gy X 10 given to a perineal field. Twenty-four patients have relapsed after their prostatic radiotherapy, only three of them within the irradiated area. For the patients with T0-T2 tumors, the 5-year crude survival was 69%, whereas it was only 37% for patients with T3 tumors. Thirty-five patients developed intestinal (26 patients) and/or urogenital (23 patients) radiation side effects. In three patients a colostomy had to be performed owing to rectal stricture or fistula. The poor survival after radiotherapy in the present series is probably due to a high incidence of unrecognized pelvic lymph node metastases. In the future only prostatic cancer patients without pelvic lymph node spread will be considered candidates for definitive radiotherapy. An optimal radiation technique is mandatory in order to avoid major radiotherapy-induced toxicity.