***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: This r and omised trial compared platinum-based to anthracycline-based chemotherapy in patients with small-cell lung cancer ( limited or extensive stage ) and ⩽2 adverse prognostic factors . Patients were r and omised to receive six cycles of either ACE ( doxorubicin 50 mg/m2 i.v . , cyclophosphamide 1 g/m2 i.v . and etoposide 120 mg/m2 i.v . on day 1 , then etoposide 240 mg/m2 orally for 2 days ) or PE ( cisplatin 80 mg/m2 and etoposide 120 mg/m2 i.v . on day 1 , then etoposide 240 mg/m2 orally for 2 days ) given for every 3 weeks . For patients where cisplatin was not suitable , carboplatin ( AUC6 ) was substituted . A total of 280 patients were included ( 139 ACE , 141 PE ) .  The response rates were 72 % for ACE and 77 % for PE . One-year survival rates were 34 and 38 % ( P=0.497 ) , respectively and 2-year survival was the same ( 12 % ) for both arms . For LD patients , the median survival was 10.9 months for ACE and 12.6 months for PE ( P=0.51 ) ; for ED patients median survival was 8.3 months and 7.5 months , respectively . More grade s 3 and 4 neutropenia ( 90 vs 57 % , P<0.005 ) and grade s 3 and 4 infections ( 73 vs 29 % , P<0.005 ) occurred with ACE , result ing in more days of hospitalisation and greater i.v . antibiotic use . ACE was associated with a higher risk of neutropenic sepsis than PE and with a trend towards worse outcome in patients with LD , and should not be studied further in this group of patients Alternating chemotherapy for small cell lung cancer has been tested in several studies . Some have shown positive results that have not been confirmed in other studies . In all of the studies , however , the degree of non-cross-resistance in the regimens was question able . The EORTC Lung Cancer Study Group developed two equipotent regimens : ( i ) st and ard (CDE)-cyclophosphamide , doxorubicin , etoposide ; ( ii ) (VIMP)-vincristine , carboplatin , ifosfamide , mesna , both non-cross-resistance . These two combinations were alternated and compared with the st and ard chemotherapy regimen in a group of 143 patients with extensive small cell lung cancer .  Median survival was 7.6 months in the st and ard arm and 8.7 in the alternating arm ( P = 0.243 ) . Median time to progression was 5.8 and 6.4 months , respectively ( P = 0.166 ) . Median response duration was 7.0 and 6.8 months ( P = 0.221 ) . The use of two alternating regimens with a proven degree of non-cross-resistance did not result in any improvement in survival in patients with extensive small cell lung cancer One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospect i ve r and omized study with the aim to assess the efficacy and tolerance of high-dose epirubicin ( 120 mg/m2 ) in combination with either cyclophosphamide ( 800 mg/m2 ; arm 1 ) or cisplatin ( 60 mg/m2 ; arm 2 ) . Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only .  The overall response rate ( CR+PR ) in arm 1 and 2 were 61.4 ( 27/44 ) and 67.3 % ( 35/52 ) , respectively . The mean duration of remission was 4.4 months ( arm 1 ) and 4.9 months ( arm 2 ) . The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2 . WHO grade 4 toxicity was encountered in 25.5 and 15.8 % of patients in arm 1 and 2 , respectively . One case of cardiotoxicity result ing in the patient 's death was observed in arm 1 . Both combinations showed considerable antitumor activity . Toxicity was acceptable PURPOSE To investigate whether chemotherapy with etoposide and cisplatin ( EP ) is superior to cyclophosphamide , epirubicin , and vincristine ( CEV ) in small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS A total of 436 eligible patients were r and omized to chemotherapy with EP ( n = 218 ) or CEV ( n = 218 ) . Patients were stratified according to extent of disease ( limited disease [ LD ] , n = 214 ; extensive disease [ ED ] , n = 222 ) . The EP group received five courses of etoposide 100 mg/m(2 ) intravenously ( IV ) and cisplatin 75 mg/m(2 ) IV on day 1 , followed by oral etoposide 200 mg/m(2 ) daily on days 2 to 4 . The CEV group received five courses of epirubicin 50 mg/m(2 ) , cyclophosphamide 1,000 mg/m(2 ) , and vincristine 2 mg , all IV on day 1 . In addition , LD patients received thoracic radiotherapy concurrent with chemotherapy cycle 3 , and those achieving complete remission during the treatment period received prophylactic cranial irradiation . RESULTS The treatment groups were well balanced with regard to age , sex , and prognostic factors such as weight loss , and performance status . The 2- and 5-year survival rates in the EP arm ( 14 % and 5 % , P = .0004 ) were significantly higher compared with those in the CEV arm ( 6 % and 2 % ) . Among LD patients , median survival time was 14.5 months versus 9.7 months in the EP and CEV arms , respectively ( P = .001 ) . The 2- and 5-year survival rates of 25 % and 10 % in the EP arm compared with 8 % and 3 % in the CEV arm ( P = .0001 ) . For ED patients , there was no significant survival difference between the treatment arms . Quality -of-life assessment s revealed no major differences between the r and omized groups . CONCLUSION EP is superior to CEV in LD-SCLC patients . In ED-SCLC patients , the benefits of EP and CEV chemotherapy seem equivalent , with similar survival time and quality of life The National Cancer Institute of Canada Clinical Trials Group conducted a prospect i ve r and omized study comparing st and ard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer .  " St and ard " treatment consisted of cyclophosphamide ( 1000 mg/m2 body surface area ) ; doxorubicin ( 50 mg/m2 ) , and vincristine ( 2 mg ) every 3 weeks for six courses . Alternating chemotherapy was cyclophosphamide , doxorubicin , and vincristine alternating with etoposide ( 100 mg/m2 on days 1 to 3 ) and cisplatin ( 25 mg/m2 on days 1 to 3 ) every 3 weeks for six treatment cycles . Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival . Best response was higher in patients on alternating chemotherapy ( complete plus partial response , 80 % compared with 63.2 % ; p less than 0.002 ) . Progression-free survival for patients on alternating chemotherapy was superior ( p less than 0.0001 ) as was overall survival ( p = 0.03 ) . Major toxicities were equally frequent in both treatment groups . These results show a modest superiority of alternating chemotherapy  over st and ard therapy  in extensive small cell lung cancer The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in design ing chemotherapy regimes . In this Southwest Oncology Group ( SWOG ) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer . The concurrent drug combination consisted of etoposide ( VP-16 ) , 75 mg/m2/intravenously ( IV ) , days 1 , 2 , and 3 ; vincristine , 1.0 mg/m2/IV , days 1 and 8 ; Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) , 40 mg/m2/IV , day 1 ; and cyclophosphamide , 750 mg/m2/IV , day 1 ( EVAC ) . The alternating combination consisted of VP-16 , 100 mg/m2/IV , days 1 , 2 , and 3 ; and cisplatin ( CDDP ) , 100 mg/m2/IV , day 1 , alternating with vincristine , 1.0 mg/m2/IV , days 1 and 8 ; Adriamycin , 50 mg/m2/IV , day 1 ; and cyclophosphamide , 750 mg/m2/IV , day 1 ( VP-16/CDDP-VAC ) . Chemotherapy was administered at 3-week intervals for six cycles both before and after chest ( 5,000 rads/5 weeks ) and whole brain radiotherapy ( 3,000 rads/2 weeks ) . One hundred ninety-nine patients received EVAC and 201 received the alternating combination . There was no significant difference in the response rate to the initial six cycles of treatment with EVAC ( CR , 40 % ) versus the alternating combination ( CR , 38 % ) . There was no significant difference between the best response , EVAC ( CR , 48 % ) and VP-16/CDDP-VAC ( CR , 51 % ) . Median survival for all r and omized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination ( P = .58 ) . Toxicities consisted primarily of bone marrow suppression , anorexia , nausea and vomiting , peripheral neuropathies , and alopecia . As in previous trials , the chest was the most common site of relapse ( 33 % ) . There were no differences in the incidence and sites of relapse between the two treatment arms . These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer The objective of this study was to evaluate the activity and toxicity of combined cisplatin , etoposide , and gemcitabine ( PEG ) and combined cisplatin plus gemcitabine ( PG ) in previously untreated patients with extensive‐stage and poor‐prognosis limited‐stage small‐cell lung carcinoma After stratification for the extent of disease , previously untreated patients with small cell lung cancer r and omized to receive therapy with the four-drug combination of cyclophosphamide , oncovin , nimustine hydrochloride ( ACNU ) , and procarbazine ( CONP ) every four weeks ( continuous regimen ) or to receive CONP alternating with the three-drug combination of etoposide ( VP-16 ) , adriamycin and cisplatin ( VAD ) at four-week intervals ( alternating regimen ) . Sixty-nine patients were entered in the study . Of 34 evaluable patients receiving the continuous regimen , six ( 17.6 % ) achieved complete response ( CR ) and 16 ( 47.1 % ) achieved partial response ( PR ) . Of 31 evaluable patients receiving the alternating regimen , 10 ( 32.3 % ) achieved CR , and 16 ( 51.6 % ) achieved PR . There was a tendency in favor of the alternating regimen in CR and over-all response rates ( 0.05 less than p less than 0.1 ) . There were no significant differences between the regimens in response duration or survival . The projected median survival times were 9.2 months and 9.4 months for the continuous and alternating regimens , respectively . One patient receiving the continuous regimen and three receiving the alternating regimen have been living for more than two years . The major toxicity was myelosuppression in both regimens . One patient died of hemorrhage due to thrombocytopenia during induction with CONP , and one patient died of cisplatin-induced renal failure . We conclude that alternating non-cross resistant chemotherapy leads to improved CR and response rates , but does not improve survival Ninety five patients with small cell carcinoma of the lung were r and omly assigned to one of two chemotherapy regimens ( VACE or CVACE ) , each consisting of six cycles at three week intervals . The VACE regimen consisted of six cycles of vincristine 1.2 mg/m2 , doxorubicin 40 mg/m2 , and cyclophosphamide 700 mg/m2 on day 1 plus etoposide 110 mg/m2 daily for three days . The CVACE regimen was identical to the VACE regimen for cycles 3 and 4 ; cycles 1 , 2 , 4 , and 6 consisted of etoposide 110 mg/m2 for three days plus cisplatin 100 mg/m2 with mannitol diuresis on the second day . Forty eight patients received VACE and 47 CVACE .  Side effects result ed in withdrawal of four patients receiving VACE and six receiving CVACE . Three deaths were attributed to VACE and one to CVACE . Median survival did not differ 
    Output:
    
There was also no statistically significant difference in terms of overall tumour response .
However , platinum-based treatment regimens did have a significantly higher rate of complete response .
Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting and thrombocytopenia toxicity .
Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens .
However , platinum-based chemotherapy regimens did increase complete response rates , at the cost of higher adverse events including nausea and vomiting , anaemia and thrombocytopenia toxicity .
These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile .
This systematic review highlights the lack of quality -of-life data in trials involving chemotherapy treatment for SCLC .
With poor long-term survival associated with both treatment groups , the issue of the quality of the survival period takes on even more significance .