***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: BACKGROUND High dose interleukin-2 therapy , administered in bolus , is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma . OBJECTIVES To present our experience using this mode of therapy in 21 patients with metastatic melanoma . MATERIAL S AND METHODS The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years ( range 29 - 63 ) . Their metastatic disease was present in all extracranial sites , dermal and sub-dermal metastases being the most common ( 15 patients had at least one site , in addition to other locations of metastases ) . Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site . Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between .  Radiological and physical evaluation was performed 6 - 8 weeks after the first course . If a response was achieved a second course of therapy was given . Patients received up to 14 planned doses of IL-2 in each week , 720,000 IU/kg of IL-2 per dose i.v . in 15 minutes . All treatments were given in the surgical ward , and only one patient was hospitalized in the intensive care unit . RESULTS Of the 21 patients , one had a complete response that has lasted for 17 months and 5 patients had a partial response ( range 3 months to 3 years ) . One patient died during treatment , and one patient who refused further treatment because of no response died a few days after completion of treatment . Prior to therapy three of the responders had received autologous vaccines with good immunological response ( P = 0.115 ) . Toxic side effects were significant , but they were treated successfully with no residual damage . CONCLUSIONS High dose IL-2 can be administered safely in a surgical department . The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients . To improve response rates , a combination of autologous vaccines prior to high dose IL-2 may be recommended Objective : To evaluate the activity of interleukin-2 ( IL-2 ) in combination with allogeneic large multivalent immunogen ( LMI ) vaccine , prepared by immobilizing SK23-CD80 + melanoma cell line plasma membrane on 5-&mgr;m-diameter silica beads , in patients with melanoma . Methods : Twenty-one patients with metastatic melanoma were r and omly assigned to an IL-2 alone control group or an IL-2 plus LMI vaccine treatment group . The primary objective was to evaluate the progression-free survival ( PFS ) of each group . Secondary clinical objectives included median overall survival ( OS ) and 1- and 2-year rates of OS . Results : Treatment was very well tolerated . Median PFS was no different between the treatment arm ( 2.20 mo ) and control arm ( 1.95 mo ) . Median OS was also similar for the treatment arm ( 11.89 mo ) and control arm ( 9.97 mo ) . Conclusions : This study failed to demonstrate that allogeneic LMI vaccine and low-dose IL-2 improved survival in patients with melanoma as compared with low-dose IL-2 alone Thus far , peptide vaccines used to stimulate tumor-specific immune responses in patients with melanoma have been largely unsuccessful . Granulocyte-macrophage colony-stimulating factor and interleukin-2 are immune-potentiating cytokines that have improved vaccine responses in pre clinical models . We hypothesized that higher doses of granulocyte-macrophage colony-stimulating factor and addition of low-dose interleukin-2 might augment responses to vaccine antigens . Patients with resected stage II , III , or IV melanoma were treated with vaccines containing three melanoma-associated peptides [ MART-1a , gp100(207–217 ) , and survivin ] , along with 300 or 500 mcg granulocyte-macrophage colony-stimulating factor in Montanide ISA . Cohorts of patients received low-dose subcutaneous interleukin-2 on days 7–20 after vaccination . Induction of a response was defined as either doubling of cytotoxic T lymphocyte frequency from baseline or increase in frequency from undetectable ( < 0.05 % ) to detectable . Leukocyte subsets and plasma cytokines were analyzed before and after vaccination . Cytotoxic T lymphocyte responses to MART-1a , gp100(207–217 ) , and survivin were induced in 11 , 16 , and 14 of 19 patients , respectively . Responses were not higher in patients receiving 500 mcg granulocyte-macrophage colony-stimulating factor or low-dose interleukin-2 than in patients receiving 300 mcg granulocyte-macrophage colony-stimulating factor only . Interleukin-2 treatment ( in nine patients ) led to increases in natural killer cells and T regulatory cells compared with no interleukin-2 treatment ( nine patients ) . Multiple plasma cytokines were transiently induced during vaccination . Neither increasing the dose of granulocyte-macrophage colony-stimulating factor nor addition of low-dose interleukin-2 result ed in an increase in the frequency of vaccine-specific cytotoxic T lymphocytes to a melanoma peptide vaccine . The increase in T regulatory cells associated with interleukin-2 treatment suggests that interleukin-2 may be immunosuppressive in this setting PURPOSE To compare the response rate , survival , and toxicity of treatment with high-dose intravenous ( IV ) bolus interleukin-2 ( IL-2 ) plus interferon alfa-2a ( IFN-alpha ) with high-dose IL-2 alone in patients with advanced melanoma in a r and omized phase III trial design . PATIENTS AND METHODS Eighty-five patients with advanced melanoma were r and omly assigned to receive IL-2 6 X 10(6 ) U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19 , or IL-2 4.5 X 10(6 ) U/m2 per dose , plus IFN-alpha 3 X 10(6 ) U/m2 using an identical schedule . A planned interim analysis was performed after 85 patients were entered , which forms the basis for this report . RESULTS Partial response ( PR ) occurred in two of 44 patients ( 5 % ; 95 % confidence interval , 1 % to 15 % ) receiving IL-2 alone , compared with four of 41 patients ( 10 % ; 95 % confidence interval , 3 % to 23 % ) receiving IL-2/IFN-alpha ( P = .30 ) . There were no complete responses ( CRs ) . The median duration of response was 11.5 months ( range , 2.0 to 15.7 + ) . There was no significant difference in the median survival duration for patients receiving IL-2 alone ( 10.2 months ) compared with patients receiving IL-2/IFN-alpha ( 9.7 months ) . The median and mean number of doses of IL-2 were equivalent in both groups , as was toxicity . There were three treatment-related deaths , two in the IL-2-alone arm and one in the IL-2/IFN-alpha arm . The trial was terminated after the first interim analysis based on predefined early-stopping rules , which included termination if the response rate in the IL-2/IFN-alpha arm was less than 25 % . CONCLUSION Using the preparation , dose , and schedule of IL-2 in our trial , IFN-alpha failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma BACKGROUND Treatment using interleukin-2 ( IL-2 ) alone or in conjunction with lymphokine-activated killer ( LAK ) cells has been shown to mediate disease regression in selected patients with advanced cancer . PURPOSE This prospect i ve r and omized trial was design ed to determine whether the administration of LAK cells in conjunction with high-dose IL-2 alters response and survival rates , compared with those for IL-2 alone , in patients with advanced cancer . METHODS The 181 patients who had metastatic cancer that had failed to respond to st and ard therapy or who had disease for which no effective therapy existed received treatment with  high-dose IL-2 alone or with LAK cells plus IL-2 . Both treatment groups were to receive the same dose of IL-2 administered according to the same schedule . IL-2 doses were omitted depending on the tolerance of the patient . Of the 181 patients , 97 had renal cell cancer and 54 had melanoma . RESULTS Median potential follow-up was 63.2 months . There were 10 complete responses among the 85 assessable patients who received IL-2 plus LAK cells , compared with four among the 79 who received IL-2 alone . There were 14 and 12 partial responses , respectively . Complete response continues in seven patients at 50 - 66 months . The 36-month actuarial survival with IL-2 plus LAK cells was 31 % , compared with 17 % with IL-2 alone ( two-sided P value [ P2 ] = .089 ) . A trend toward improved survival was seen for patients with melanoma who received IL-2 plus LAK cells , compared with those who received IL-2 alone ( 24-month survival : 32 % versus 15 % ; 48-month survival : 18 % versus 4 % ; P2 = .064 [ corrected ] ) . None of 26 patients with melanoma who received IL-2 alone are alive ; five of 28 who received IL-2 plus LAK cells are alive , and three continue in complete response . No difference in survival was seen in patients with renal cell cancer in the two treatment groups . There were six treatment-related deaths ( 3.3 % ) ; three were due to myocardial infa rct ion . Other toxic effects resolved by discontinuation of IL-2 . Many toxic effects were related to increased vascular permeability induced by IL-2 . CONCLUSIONS Some patients with metastatic cancer have prolonged remission when they are treated with high-dose IL-2 alone or in conjunction with LAK cells . Our results suggest a trend toward increased survival when IL-2 is given with LAK cells in patients with melanoma , but no trend was observed for patients with renal cell cancer . IMPLICATION S As these studies continue , efforts are underway to develop improved immunotherapies using tumor-infiltrating lymphocytes ( TIL ) and gene-modified TIL BACKGROUND Objective tumor response is a common endpoint in daily practice as well as in clinical trials to evaluate the efficacy of anti-cancer agents . Traditionally , the st and ard World Health Organization ( WHO ) criteria has been adopted in these context s. However , the recent development of new classes of anti-cancer agents and progress in imaging technology have required new methodology to evaluate response to treatment . Recently , the Response Evaluation Criteria in Solid Tumors Group ( RECIST ) proposed new guidelines using unidimensional measurement . Theoretically , the simple sum of the maximum diameters of individual tumors is more linearly related to cell kill than is the sum of the bidimensional products . To vali date these new guidelines , we have compared the st and ard WHO response criteria with the new RECIST guidelines in the same patient population . METHODS Data from 79 patients enrolled in eight prospect i ve phase II studies at Samsung Medical Center were retrospectively re-analyzed to determine the concordance between the two response criteria . The two response criteria were applied separately , and the results were compared using the kappa statistic to test concordance for overall response rate . RESULTS The overall response rate according to the WHO criteria was 31.6 % . Using the RECIST criteria , nine patients were reclassified and the overall response rate was 30.4 % . There was excellent agreement between the unidimensional and bidimensional criteria in 23 of 25 responses ( 92 % ) . The kappa statistic for concordance for overall response was 0.91 . CONCLUSIONS We conclude that the new RECIST guidelines are comparable to the old response criteria in evaluating response in solid tumors . Moreover , the new guidelines are just as simple and reproducible in the measurement of response in daily practice as they are in clinical trials Tumour-infiltrating lymphocytes ( TIL ) were isolated and exp and ed from small tumour biopsy sample s of twenty-eight patients ( thirteen with malignant melanoma , seven with renal cell carcinoma , and eight with non-small-cell lung cancer ) . The patients were treated with autologous exp and ed TIL ( about 10(10 ) ) and continuous infusions of recombinant human interleukin-2(1 - 3 x 10(6 ) U/m2 per 24 h ) . 29 % of the patients with renal cell cancer and 23 % of those with melanoma achieved objective tumour responses lasting 3 - 14 months . Toxic side-effects were limited , and no patient required intensive-care monitoring . Adoptive immunotherapy with TIL and interleukin-2 may be an effective systemic approach to the treatment of some patients with malignant melanoma and renal cell carcinoma BACKGROUND The safety and efficacy of immunotherapy with histamine dihydrochloride ( HDC ) , interleukin-2 ( IL-2 ) and interferon-alpha2b ( IFN ) compared with dacarbazine ( DTIC ) in adult patients with stage IV melanoma was evaluated . PATIENTS AND METHODS Two hundred and forty-one patients were r and omized to either receive repeated 4- 
    Output:
    
High and intermediate-IL-2 dosage showed no CR difference , while low-dose IL-2 showed a nonstatistical trend toward an increased CR rate .
The significance is that , contrary to popular belief , the data demonstrated that CR rates were similar for intermediate versus high-IL-2 dosing