***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A national cooperative group trial was conducted in 153 patients with chronic myelogenous leukemia ( CML ) in chronic phase treated with oral pulse busulfan  to determine if oral vitamin A can increase the time to blast crisis and enhance survival of patients . Patients diagnosed within 1 year and in the chronic phase of CML were r and omized to receive oral pulse busulfan or the alkylator plus continuous oral vitamin A. Distributions of clinical progression and overall survival were estimated using the method of Kaplan and Meier . Associations of these endpoints with treatment and other patient characteristics were analyzed using the proportional hazards regression method of Cox . Both regimes were well tolerated . Patients in the busulfan plus vitamin A arm had somewhat longer duration s of clinical progression-free survival ( median 46 months ) and overall survival ( 51 months ) compared to those in the busulfan arm ( medians 38 and 44 months ) . However , the differences were not statistically significant ( one-tailed P = 0.11 for clinical progression-free survival , 0.081 for survival ) . After adjustment for significant factors identified in an additional exploratory multivariate analysis , risk of clinical progression or death was 53 % ( P = 0.022 ) greater and risk of death 60 % ( P = 0.014 ) greater among busulfan patients . Given the relatively large though non-significant difference between treatment arms , the limited statistical power of the study , and the likelihood that oral vitamin A may not be the most effective means of delivering retinoid therapy , we conclude that further investigation of retinoids in chronic phase CML is warranted Ratios of urinary 8‐hydroxy‐2′‐deoxyguanosine to urinary creatinine ( 8‐OHdG/creatinine ) have been considered as a good biological indicator of DNA oxidation . Urinary 8‐OHdG/creatinine levels of lung cancer patients were evaluated by enzyme‐linked immunosorbent assay using a monoclonal antibody N45.1 during radiotherapy and chemotherapy . An increase in urinary 8‐OHdG/creatinine was found in non‐small‐cell carcinoma ( non‐SCC ) patients during the course of radiotherapy .  SCC patients showed higher levels of urinary 8‐OHdG/creatinine than the controls . Furthermore , SCC patients with complete or partial response to the chemotherapy showed a significant decrease in urinary 8‐OHdG/creatinine while patients with no change or progressive disease showed an increase PURPOSE Glutathione has been shown to be an effective chemoprotector against cisplatin-induced side effects in patients with ovarian cancer . In view of this fact , we performed a r and omized clinical pilot-trial in the management of other solid tumors in order to compare application of Glutathione to intensive hydration in patients undergoing chemotherapy with a regimen including cisplatin .  PATIENTS AND METHODS Twenty patients suffering from advanced non small cell lung cancer ( n = 6 ) or head- and neck cancer ( n = 14 ) were enrolled in the study . All patients received 80 mg/m2 cisplatin along with etoposide or 5-fluorouracil every 4 weeks . Patients r and omized to application of Glutathione ( n = 11 ) received 5 g of Glutathione immediately before application of cisplatin followed by 2000 ml of normal saline . Patients in the control group ( n = 9 ) received 2000 ml electrolyte infusion before and 2000 ml of normal saline with forced diuresis after cisplatin . RESULTS The intensity of hematologic toxicity was significantly less pronounced in patients treated with Glutathione than in the control group ( hemoglobin : 10.7 vs 9.5 mg% respectively , p = 0.039 ; white blood cell count 3.3 vs 2.2 x 103/microliter respectively , p = 0.004 ; platelets 167 vs 95 x 103/microliter respectively , p = 0.02 ) , whereas in terms of non-hematologic toxicity no difference was observed . Objective remission occurred in 6 out of 11 evaluable patients from the group receiving Glutathione ( 55 % ; complete remission : 9 % ; partial remission : 46 % ) , and in 4 out of 8 evaluable patients from the control group ( partial remission : 50 % ) . However , there was no statistical difference in terms of response and overall survival ( 13.5 months vs. 10.5 months ) between the two groups . CONCLUSIONS Application of Cisplatin and Glutathione seems to be safe and feasible and the antitumoral efficacy of cisplatin is apparently not impaired by the concomitant use of Glutathione in patients with solid tumors BACKGROUND Early clinical trials have suggested that glutathione ( GSH ) offers protection from the toxic effects of cisplatin . PATIENTS AND METHODS One hundred fifty-one patients with ovarian cancer ( stage I-IV ) were evaluated in a clinical trial of cisplatin ( CDDP ) + /- glutathione ( GSH ) . The objective was to determine whether GSH would enhance the feasibility of giving six cycles of CDDP at 100 mg/m2 without dose reduction due to toxicity . RESULTS When considering the proportion of patients receiving six courses of CDDP at any dose , GSH produced a significant advantage over control--58 % versus 39 % , ( P = 0.04 ) . For these patients there was a significant difference between the reduction in creatinine clearance for GSH treated patients compared with control--74 % versus 62 % ( P = 0.006 ) . Quality of life scores demonstrated that for patients receiving GSH there was a statistically significant improvement in depression , emesis , peripheral neurotoxicity , hair loss , shortness of breath and difficulty concentrating . As an indication of overall activity , these patients were statistically significantly more able to undertake housekeeping and shopping . Clinical ly assessed response to treatment demonstrated a trend towards a better outcome in the GSH group ( 73 % versus 62 % ) but this was not statistically significant ( P = 0.25 ) . CONCLUSIONS The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient 's quality of life is improved Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage . In addition , melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production . On this basis , we have performed a r and omized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients ( NSCLC ) with poor clinical status . The study included 70 consecutive advanced NSCLC patients who were r and omized to receive chemotherapy alone with cisplatin ( 20 mg/m2/day i.v . for 3 days ) and etoposide ( 100 mg/m2/day i.v . for 3 days ) or chemotherapy plus melatonin ( 20 mg/day orally in the evening ) . Cycles were repeated at 21-day intervals . Clinical response and toxicity were evaluated according to World Health Organization criteria . A complete response ( CR ) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone . Partial response ( PR ) occurred in 10/34 and in 6/36 patients treated with or without melatonin , respectively . Thus , the tumor response rate was higher in patients receiving melatonin ( 11/34 vs. 6/35 ) , without , however , statistically significant differences . The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone ( 15/34 vs. 7/36 , P < 0.05 ) . Finally , chemotherapy was well tolerated in patients receiving melatonin , and in particular the frequency of myelosuppression , neuropathy , and cachexia was significantly lower in the melatonin group . This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy , mainly in terms of survival time , and reduce chemotherapeutic toxicity in advanced NSCLC , at least in patients in poor clinical condition Summary In two groups of female patients with metastatic breast cancer who had all been pretreated with doxorubicin ( 350 mg/m2 ) , acute cardiac effects following i.v . doxorubicin bolus injection ( 60 mg/m2 ) were recorded on the basis of systolic time intervals ( STI ) . In six patients who received doxorubicin only the ratio between the heart-beat-corrected preejection period and left ventricular ejection time ( PEPI : LVETI ) as well as the PEP index were found to be significantly increased with a peak at 6 h following drug infusion ( P<0.001 ) . Another six patients received an identical chemotherapeutic regimen and , in addition , a combination of tocopherol ( 200 mg i.m . 6 h before treatment ) and nifedipine ( 60 mg p.o . daily from 2 days before doxorubicin infusion ) . In the pretreatment group , the PEPI : LVETI ration and PEP index remained unchanged during the posttreatment period . Pharmacokinetic analysis of drug concentrations in the plasma revealed a significantly accelerated distribution and elimination of doxorubicin  after combined tocopherol and nifedipine pretreatment , although no statistically significant differences could be found in calculated drug levels in the peripheral compartment between both treatment groups . Our results indicate that acute cardiac reactions reflected by changes in STI values can be prevented by combined tocopherol and nifedipine pretreatment Objective : In vitro and animal studies suggest that antitumor effect of chemotherapeutic agents may be enhanced by antioxidants . Therefore , we initiated a clinical study to test the efficacy of high-dose multiple antioxidants ( vitamins C , E and beta carotene ) as an adjunct to chemotherapy ( paclitaxel and carboplatin ) in non-small-cell lung cancer . Methods : 136 patients of stage IIIb and stage IV NSCLC were r and omized to receive chemotherapy ( paclitaxel and carboplatin ) alone  ( chemotherapy arm , n = 72 ) or chemotherapy in combination with ascorbic acid 6100 mg/day , dl-alpha-tocopherol ( vitamin E ) 1050 mg/day and beta-carotene 60 mg/day ( combination arm , n = 64 ) . Survival were calculated by the Kaplan-Meier method and compared using the log-rank test . Results : An overall response rate ( RR ) of 33 % was observed in chemotherapy arm with 24 patients showing a partial response ( PR ) and none showing a complete response ( CR ) . In combination arm the overall RR was 37 % with 24 patients showing PR and two showing CR . The median survival times in chemotherapy arm and combination arm were nine and 11 months respectively . The overall survival ( OS ) rates in chemotherapy arm and combination arm at one year were 32.9 % and 39.1 % , and at two years , 11.1 % and 15.6 % respectively . None of these differences were statistically significant ( p = 0.20 ) . Toxicity profiles were similar in both arms . Conclusions : These results do not support the concern that antioxidants might protect cancer cells from the free radical damage induced by chemotherapy . Larger trials are needed to demonstrate whether high-dose multiple antioxidants in conjunction with chemotherapy increase the response rates and /or survival time in advanced lung cancer Cisplatin-induced toxicities are mainly caused by the formation of free radicals , leading to oxidative organ damage . Plasma concentrations of antioxidants decrease significantly during cisplatin chemotherapy for cancer . Forty-eight cancer patients treated with cisplatin-based chemotherapy  were r and omised in a double-blind manner to receive either supplementation with vitamin C , vitamin E and selenium dissolved in a beverage or to receive a placebo beverage . Primary outcome measures were the amount of nephrotoxicity and ototoxicity induced by cisplatin . No significant differences were found between the two study groups with respect to these primary outcome measures . However , patients who achieved the highest plasma concentrations of the three antioxidant micronutrients had significantly less loss of high-tone hearing . In addition , significant correlations were found between the reduced/oxidised vitamin C ratio and malondialdehyde ( MDA ) , markers of oxidative stress , and cisplatin-induced ototoxicity and nephrotoxicity . The lack of protection against cisplatin-induced toxicities in patients in the intervention arm may be related to poor compliance and /or inadequate supplementation . Supplementation with a higher dose ( intensity ) and in combination with other antioxidants should be investigated further PURPOSE We performed a r and omized , double-blind , placebo-controlled trial to assess the efficacy of glutathione ( GSH ) in the prevention of oxaliplatin-induced neurotoxicity . PATIENTS AND METHODS Fifty-two patients treated with a bimonthly oxaliplatin-based regimen  were r and omized to receive GSH ( 1,500 mg/m(2 ) over a 15-minute infusion period before oxaliplatin ) or normal saline solution .  Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four ( oxaliplatin dose , 400 mg/m(2 ) ) , eight ( oxaliplatin dose , 80 
    Output:
    
CONCLUSION None of the trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy .