***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 St and ard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination . The Gynecologic Oncology Group conducted a r and omized , phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer . METHODS We r and omly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 ( intravenous-therapy group ) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 ( intraperitoneal-therapy group ) . Treatment was given every three weeks for six cycles . Quality of life was assessed . RESULTS Of 429 patients who underwent r and omization , 415 were eligible .  Grade 3 and 4 pain , fatigue , and hematologic , gastrointestinal , metabolic , and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group ( P < or = 0.001 ) . Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy , but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months , respectively ( P=0.05 by the log-rank test ) . The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months , respectively ( P=0.03 by the log-rank test ) . Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment . CONCLUSIONS As compared with intravenous paclitaxel plus cisplatin , intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer BACKGROUND We aim ed to evaluate the in vitro and in vivo effects of poly [ L-lactic acid ] microsphere containing cisplatin ( CDDP-MS ) for intraperitoneal ( i.p . ) chemotherapy for ovarian cancer . METHODS We initially examined the in vitro and in vivo profile of cisplatin release from the CDDP-MS , then this drug delivery system was evaluated in 15 patients . RESULTS The in vitro study showed that cisplatin was released constantly over a 3-week period . Rats in the CDDP-MS group had a significantly lower peak serum concentration of platinum compared with rats in the aqueous cisplatin solution ( CDDP-S ) group ; the serum concentration of platinum showed a gradual decline . The ascitic fluid concentration of platinum also gradually decreased in the CDDP-MS group . We treated 15 patients with recurrent ovarian cancer with CDDP-MS containing 200 mg of cisplatin ( n = 5 ) or CDDP-S containing 100 mg of cisplatin ( n = 10 ) administered i.p . The peak serum and ascites concentrations of platinum were lower immediately after administration of CDDP-MS than after administration of CDDP-S , but increased over time in the CDDP-MS group , reflecting the slow-release effect of CDDP-MS . Grade 1 to 2 leukopenia and /or neutropenia occurred in 2 of 5 patients . No thrombocytopenia or renal or neurologic toxicity was observed ; CONCLUSION These findings indicate that the i.p . administration of CDDP-MS increased the dose intensity of cisplatin and appeared to be safe and effective for the treatment of ovarian cancer Pegylated liposomal doxorubicin is a new formulation with activity against epithelial ovarian carcinoma ( EOC ) . The authors sought to determine patient characteristics that may predict for response to this treatment and favorable  time to failure as well as survival BACKGROUND Cisplatin is a highly effective chemotherapeutic agent against epithelial ovarian cancer but is associated with significant toxicities . SPI-77 is a liposomal pegylated formulation of cisplatin that was developed to reduce systemic toxicity and to better deliver cisplatin to tumors . We assessed the response rates and safety of SPI-77 , in patients with recurrent epithelial ovarian cancer . PATIENTS AND METHODS Patients were selected for having previously achieved a platinum treatment free interval of greater than 6 months ( e.g. platinum-sensitive ) and high potential of achieving responses when rechallenged with a platinum drug . SPI-77 was administered at a dose of 260 mg/m(2 ) every 21 days until disease progression . RESULTS Enrollment was terminated after 5 patients were treated because of concern with the adequacy of the formulation . Four out of the five patients had stable disease as best response . While no serious , unexpected adverse events occurred in spite of large cumulative doses of SPI-77 , there were concerns related to the large lipid load and prolonged persistence of residual platinum in body stores . CONCLUSION The results of this study , although inconclusive regarding its primary endpoints , provide some important lessons for the development of similar liposomal platinum agents PURPOSE The purpose of our studies was to define the maximal-tolerated dose of liposomal doxorubicin ( DOX-SL ; Liposome Technology Inc , Menlo Park , CA ) , a doxorubicin formulation of polyethyleneglycol-coated liposomes , characterize the toxicities associated with this formulation , and evaluate any indication of antitumor activity within a phase I setting . PATIENTS AND METHODS Two separate phase I studies were conducted following the initial human pharmacokinetic testing at one of the sites ( Hadassah ) . The starting dose of 20 mg/m2 at the University of Southern California was just below the dose without toxicity in the pharmacokinetic study . At Hadassah , the phase I starting dose was just above their earlier safe single doses , 60 mg/m2 . Both studies involved cohorts of at least three patients and redosing every 3 to 4 weeks . To determine the recommended dose for phase II trials , an additional level of 50 mg/m2 every 3 weeks was explored , and the level of 60 mg/m2 every 4 weeks was exp and ed . RESULTS A total of 56 patients receiving 281 courses of DOX-SL was accrued and evaluated for toxicity . H and -foot ( H-F ) syndrome and stomatitis are the two main dose-limiting factors of DOX-SL .  Stomatitis was dose-limiting for high single doses of DOX-SL greater than 70 mg/m2 . Skin toxicity manifested primarily as H-F syndrome was dose-limiting for repetitive dosing , but acceptable at either 50 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks . Attenuation of acute subjective symptoms and lack of alopecia were generally observed . Patients with carcinomas of the breast , ovary , prostate , and head and neck were among those showing objective antitumor responses or improvement based , in part , on blood levels of tumor markers . CONCLUSION The toxicity profile of DOX-SL differs prominently from that of the free drug administered by bolus or rapid infusion and with some differences , resembles that of prolonged continuous infusion . This finding , as well as the antitumor activity observed , supports wide phase II testing of DOX-SL in solid tumors PURPOSE Stealth liposomal doxorubicin ( Alzal Corp , Palo Alto , CA ) has a slower clearance rate than free doxorubicin , result ing in sustained serum levels . Liposomal encapsulation also leads to increased concentration of drug in tumor tissue . Meta- analysis of previous studies has shown that doxorubicin has activity in epithelial ovarian cancer . The current study was developed to examine the activity of Stealth liposomal doxorubicin in platinum- and paclitaxel-refractory ovarian cancer . PATIENTS AND METHODS Patients had epithelial ovarian cancer that either progressed on or recurred within 6 months of completion of platinum and paclitaxel chemotherapy . All patients had measurable disease .  Stealth liposomal doxorubicin was administered at 50 mg/m(2 ) every 4 weeks as a 1-hour infusion . RESULTS Eighty-nine patients were treated and included in an intent-to-treat analysis . There were 82 patients who were platinum and paclitaxel refractory and met all study criteria . There was one complete response and 14 partial responses , for a total response rate of 16.9 % ( 95 % confidence interval [ CI ] , 9.1 % to 24.6 % ) . For platinum- and paclitaxel-refractory patients , the response rate was 18.3 % ( 95 % CI , 9.9 % to 26.7 % ) . Median time to progression was 19 . 3 weeks for the entire population . Ten patients ( 11.2 % ) withdrew because of adverse events related to the drug ( palmar-plantar erythrodysesthesia [ PPE ] , n = 3 ; asthenia , n = 2 ; cardiac , n = 2 ; neutropenia , n = 1 ; stomatitis , n = 1 ; and edema , n = 1 ) . There were no drug-related fatal events . There were only eight grade 4 adverse events attributable to the drug . Stomatitis , PPE , and skin lesions were managed with dose reductions and delays in most cases . CONCLUSION Stealth liposomal doxorubicin has activity in refractory epithelial ovarian cancer . PPE and stomatitis can usually be managed by dose adjustment . The ease of administration makes this an attractive agent PURPOSE A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens .  Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study . PATIENTS AND METHODS Thirty-five consecutive patients were accrued in two institutions ( 22 in one and 13 in the other ) . All had progressive disease after either cisplatin or carboplatin and paclitaxel , or at least one platinum-based and one paclitaxel-based regimen .  Patients received intravenous ( I.V. ) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities , or a lengthening of the interval to 4 weeks ( and occasionally to 5 weeks ) with persistence of grade 1 or 2 toxicities beyond 3 weeks . RESULTS Nine clinical responses ( one complete response [ CR ] , eight partial responses [ PRs ] ) were observed in 35 patients ( 25.7 % ) , with seven of these having been confirmed by two consecutive computed tomographic ( CT ) measurements . The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24 + months ( median , 11 months ) . Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities ( either h and -foot syndrome or stomatitis ) , with dose modifications , the treatment was very well tolerated . Nausea that was clearly attributable to the drug , hair loss , extravasation necrosis , or decreases in ejection fraction did not occur . CONCLUSION Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel . The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity . This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients BACKGROUND Primary debulking surgery before initiation of chemotherapy has been the st and ard of care for patients with advanced ovarian cancer . METHODS We r and omly assigned patients with stage IIIC or IV epithelial ovarian carcinoma , fallopian-tube carcinoma , or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery ( so-called interval debulking surgery ) . RESULTS Of the 670 patients r and omly assigned to a study treatment , 632 ( 94.3 % ) were eligible and started the treatment . The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery ( metastatic lesions that were larger than 5 cm in diameter in 74.5 % of patients and larger than 10 cm in 61.6 % ) . The largest residual tumor was 1 cm or less in diameter in 41.6 % of patients after primary debulking and in 80.6 % of patients after interval debulking . Postoperative 
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In the majority of the included studies chemotherapeutics entrapped in a DDS significantly improved efficacy over free chemotherapeutics regarding both survival and tumor growth inhibition .
Subgroup analyses , however , revealed that cisplatin entrapped in a DDS did not result in additional tumor growth inhibition compared to free cisplatin , although it did result in improved survival .
Micelles did not show a significant tumor growth inhibition compared to free chemotherapeutics , which indicates that micelles may not be a suitable DDS for ovarian cancer treatment .
Other subgroup analyses , such as targeted versus non-targeted DDS or IV versus IP administration route , did not identify specific characteristics of DDS that affected treatment efficacy .
This systematic review shows the potential , but also the limitations of chemotherapy by drug delivery systems for ovarian cancer treatment .