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              Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut 
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              1: Cancer. 2000 Jul 1; 89(1): 177-80. Related Articles, Links 

          
        The efficacy of a combination of etoposide, ifosfamide, and cisplatin in 
        the treatment of patients with soft tissue sarcoma.

        Papai Z, Bodoky G, Szanto J, Poller I, Rahoty P, Eckhardt S, Lang I, 
        Szendroi M.

        Department of Chemotherapy, National Institute of Oncology, Budapest, 
        Hungary.

        BACKGROUND: Successful chemotherapy for patients with soft tissue 
        sarcoma (STS) has been limited by a lack of active drugs. The most 
        effective single agents are doxorubicin, dacarbazine, and, more 
        recently, ifosfamide. Previously the most widely used combination has 
        been CYVADIC (cyclophosphamide, vincristine, doxorubicin, and 
        dacarbazine). In one randomized trial, ifosfamide was superior to 
        cyclophosphamide; two nonrandomized studies also reported favorable 
        results. Etoposide monotherapy was successful in 8%; the effectiveness 
        of cisplatin was 5-23%. In view of these findings, the authors treated 
        STS patients with an etoposide, cisplatin, and ifosfamide (VIP) 
        combination. METHODS: The eligibility criteria included histologically 
        confirmed, inoperable, metastatic or locally recurrent STS; a World 
        Health Organization (WHO) performance status of 0-2; a maximum age of 75 
        years; and progressive, measurable disease. A total of 104 patients were 
        treated from January 1990 to June 1997. The median age of the patients 
        was 42.4 years. The patients were treated with a combination of 
        etoposide (100mg/m(2) for 5 days), ifosfamide (2000 mg/m(2) for 2 days), 
        and cisplatin (20mg/m(2) for 5 days) once a month via a peripheral vein. 
        The treatment response and the toxicity were assessed according to WHO 
        criteria. RESULTS: Of 104 evaluable patients, 47 responded. The overall 
        response rate was 46% (complete response: 10%; partial response: 36%). 
        In 43 patients the disease remained stable (41%). Remission duration was 
        4.6 months. Toxicity was moderate. The main adverse events were alopecia 
        (100%), nausea and vomiting (73%), and leukopenia (29%). CONCLUSIONS: 
        This new combination is promising for the treatment of patients with 
        advanced STS. Copyright 2000 American Cancer Society.

        Publication Types: 
          Clinical Trial

        PMID: 10897015 [PubMed - indexed for MEDLINE] 




              2: Am J Clin Oncol. 1995 Aug; 18(4): 282-6. Related Articles, 
              Links 


        Impact on progression-free survival of adjuvant cyclophosphamide, 
        vincristine, doxorubicin (adriamycin), and dacarbazine (CYVADIC) 
        chemotherapy for stage I uterine sarcoma. A prospective trial.

        Hempling RE, Piver MS, Baker TR.

        Department of Gynecologic Oncology, Roswell Park Cancer Institute, 
        Buffalo, New York 14263, USA.

        To assess the impact on progression-free survival of the use of the 
        multiagent chemotherapy regimen of cyclophosphamide, vincristine, 
        doxorubicin (Adriamycin), and dacarbazine (CYVADIC) as adjuvant 
        treatment for patients with stage I uterine sarcoma: 20 evaluable 
        patients who underwent total abdominal hysterectomy and bilateral 
        salpingo-oophorectomy for stage I uterine sarcoma received adjuvant 
        multiagent chemotherapy with vincristine sulfate 1 mg/m2 days 1 and 4, 
        doxorubicin (Adriamycin) 40 mg/m2 and cyclophosphamide 400 mg/m2 day 2, 
        and dacarbazine 200 mg/m2 days 1 through 4 for a total of 9 monthly 
        cycles or until recurrence of disease was documented. Patients were 
        followed for a median of 65 months (range: 5-116 months). Myelotoxicity 
        was monitored by weekly complete blood counts, cardiac toxicity by 
        monthly radionuclide angiography, and neurotoxicity by monthly physical 
        examination. Survival and progression-free survival were calculated by 
        the method of Kaplan and Meier (17). The Fisher exact test was employed 
        to determine the significance of recurrence rates between histologic 
        groups (18). These 20 patients received 172 of a planned 180 cycles of 
        chemotherapy. Dose reductions in response to myelotoxicity were 
        necessitated in four cycles among three patients. Mild neurotoxicity was 
        observed in six patients (30%) and moderate neurotoxicity in one patient 
        (5%). A decrease in cardiac ejection fraction of > 10% was observed in 
        two patients (10%). No deaths ascribable to complications arising from 
        chemotherapy were observed. Seven patients (35%) developed recurrence of 
        disease. Recurrence rates for pure sarcomas and mixed mesodermal tumors 
        did not differ significantly (P = .65). Progression-free survival for 
        the population at 2 years was 80% and at 5 years was 65%. This study 
        describes the largest prospective trial of adjuvant combination 
        chemotherapy for patients with stage I uterine sarcoma reported to date. 
        Adjuvant chemotherapy employing the combination of cyclophosphamide, 
        vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) failed 
        to impact significantly on long-term survival in this group of patients 
        with stage I uterine sarcoma.

        Publication Types: 
          Clinical Trial

        PMID: 7625366 [PubMed - indexed for MEDLINE] 




              3: J Clin Oncol. 1995 Jul; 13(7): 1537-45. Related Articles, Links 



        Comment in: 
          J Clin Oncol. 1995 Jul;13(7):1531-3.

        Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in 
        first-line treatment of advanced soft tissue sarcomas: a randomized 
        study of the European Organization for Research and Treatment of Cancer 
        Soft Tissue and Bone Sarcoma Group.

        Santoro A, Tursz T, Mouridsen H, Verweij J, Steward W, Somers R, Buesa 
        J, Casali P, Spooner D, Rankin E, et al.

        Divisione Oncologia Medica A, Istituto Nazionale Tumori, Milano, Italy.

        PURPOSE: The aim of this trial was to compare the activity and toxicity 
        of single-agent doxorubicin with that of two multidrug regimens in the 
        treatment of patients with adult advanced soft tissue sarcomas. PATIENTS 
        AND METHODS: This was a prospective randomized phase III trial performed 
        by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of 
        the European Organization for Research and Treatment of Cancer (EORTC). 
        Six hundred sixty-three eligible patients were randomly allocated to 
        receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, 
        vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or 
        ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C). RESULTS: The 
        overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) 
        among eligible patients and 26% among assessable patients. No 
        statistically significant difference was detected among the three study 
        arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 
        28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm 
        B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm 
        A, 51 weeks on arm B, and 55 weeks on arm C). The degree of 
        myelosuppression was significantly greater for the combination of 
        ifosfamide and doxorubicin than for the other two regimens. 
        Cardiotoxicity was also more frequent in this arm, but other toxicities 
        were similar. CONCLUSION: In advanced soft tissue sarcomas of adults, 
        single-agent doxorubicin is still the standard chemotherapy against 
        which more intensive or new drug treatments should be compared. 
        Combination chemotherapy cannot be recommended outside a controlled 
        clinical trial with the exclusion of some subsets of sarcoma patients 
        for whom significant tumor volume reduction may be an important end 
        point of a chemotherapy regimen.

        Publication Types: 
          Clinical Trial 
          Clinical Trial, Phase III 
          Multicenter Study 
          Randomized Controlled Trial 

        PMID: 7602342 [PubMed - indexed for MEDLINE] 




              4: J Clin Oncol. 1994 Jun; 12(6): 1137-49. Related Articles, Links 



        Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced 
        local recurrence but no improvement in survival: a study of the European 
        Organization for Research and Treatment of Cancer Soft Tissue and Bone 
        Sarcoma Group.

        Bramwell V, Rouesse J, Steward W, Santoro A, Schraffordt-Koops H, Buesa 
        J, Ruka W, Priario J, Wagener T, Burgers M, et al.

        London Regional Cancer Centre, Canada.

        PURPOSE: To evaluate the benefit of adjuvant chemotherapy in adult 
        patients with soft tissue sarcomas. The principal end points were 
        freedom from local recurrence and/or metastases and overall survival. 
        PATIENTS AND METHODS: Between January 1977 and June 1988, 468 patients 
        entered this randomized study and 317 were considered eligible. 
        Following complete surgical resection with or without radiotherapy, 
        outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 
        intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 
        1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 
        IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion 
        on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses 
        was compared with that in 172 control patients. RESULTS: With a median 
        follow-up duration of 80 months (range, 39 to 165), actuarial percentage 
        survival figures at 7 years were compared. Relapse-free survival rates 
        were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence 
        was significantly reduced in the CYVADIC arm at 17% versus 31% (P = 
        .004). In contrast, distant metastases occurred with similar frequency 
        in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), 
        and overall survival rates were not significantly different at 63% 
        versus 56% (P = .64). A reduction in local recurrence was only apparent 
        in the group of head, neck, and trunk sarcomas (P = .002), but not in 
        limb tumors (P = .31). CONCLUSION: Adjuvant chemotherapy with CYVADIC 
        cannot be recommended outside the context of a clinical trial. 
        Experience from this study has been used to plan a trial of neoadjuvant 
        chemotherapy with doxorubicin/ifosfamide, which is currently in 
progress.

        Publication Types: 
          Clinical Trial 
          Randomized Controlled Trial 

        PMID: 8201375 [PubMed - indexed for MEDLINE] 




              5: Cancer Chemother Pharmacol. 1993; 31 Suppl 2: S199-203. Related 
              Articles, Links 


        Feasibility study of postoperative adjuvant chemotherapy and 
        radiotherapy for soft-tissue sarcoma.

        Fuchs R, Schadeck-Gressel C, Makoski HB, von Andrian-Werburg HF, 
        Knieriem HJ, Westerhausen M.

        Klinik fur Hamatologie/Onkologie, St. Antonius-Hospital, Eschweiler, 
        Federal Republic of Germany.

        In a nonrandomized trial, postoperative, adjuvant, combined chemotherapy 
        and radiotherapy were given to 17 patients with high-grade soft-tissue 
        sarcomas. All patients had undergone conservative limb-sparing surgery. 
        Soft-tissue sarcomas were localized in the extremities (13 patients), 
        superficial trunk (3), and neck (1). In all, 13 patients received 50 
        mg/m2 doxorubicin and 5 g/m2 ifosfamide with mesna uroprotection for a 
        total of 6 cycles and 4 patients received CYVADIC 
        (cyclophosphamide/vincristine/doxorubicin/dacarbazine). Chemotherapy was 
        started immediately after wound healing. Irradiation using the 
        shrinking-field technique was commenced 3-7 days following chemotherapy; 
        a total dose of 65 Gy was applied. The major side effects of 
        chemotherapy were nausea and vomiting [17 of 17 patients, 5 experiencing 
        World Health Organization (WHO) grade 3 toxicity and 1, WHO grade 4], 
        leukopenia of <3.0 x 10(9)/l (17 patients), and leukopenia of <1.0 x 
        10(9)/l (7 patients). The median leukocyte nadir was reached on day 11 
        (range, days 7-16). The duration of critical leukopenia did not exceed 1 
        week. Reversible alopecia occurred in all patients. Temporary 
        cardiomyopathy was recorded in 1 patient. Following radiotherapy, 11 
        episodes of epitheliolysis and 1 case of moderate lymphedema were 
        documented. There was no life-threatening condition. After a follow-up 
        of 58 months, the outcome was as follows: disease-free survival, 9 
        patients; distant metastases, 7; local recurrence, 1. Excluding 3 
        patients who entered the study after undergoing surgery for local 
        relapse, the rate of distant metastases was 36%. In summary, the 
        postoperative use of chemotherapy/radiotherapy is feasible, producing 
        relevant but manageable toxicity. This combination results in effective 
        local tumor control with good functional results following limb-sparing 
        surgery. The incidence of distant metastases, however, is high.

        PMID: 8453698 [PubMed - indexed for MEDLINE] 




              6: Semin Oncol. 1992 Feb; 19(1 Suppl 1): 14-8. Related Articles, 
              Links 


        Experience with ifosfamide in the EORTC Soft Tissue and Bone Sarcoma 
        Group.

        Blackledge G, Steward WP, Verweij J, Mouridsen H, Bramwell V, Schutte J, 
        van Oosterom A, Dombernowsky P, Buesa J, Van Glabekke M, et al.

        University of Birmingham, UK.

        The Soft Tissue and Bone Sarcoma Group of the European Organization on 
        Research and Treatment of Cancer has conducted a number of studies of 
        chemotherapy in advanced disease over the past 15 years. Following the 
        discovery that the CYVADIC regimen 
        (cyclophosphamide/vincristine/doxorubicin/dimethyl imidazole 
        carboxamide) was less active than had been reported originally, the 
        individual components of CYVADIC were studied. This showed that 
        doxorubicin had considerable activity and that ifosfamide 5 g/m2 given 
        over 24 hours was at least as active as cyclophosphamide. Subsequent 
        studies have therefore centered on a combination of doxorubicin and 
        ifosfamide. A large randomized trial showed no significant benefit of 
        doxorubicin/ifosfamide over single-agent doxorubicin, but the doses of 
        doxorubicin were different. More recently, using bone marrow growth 
        factors, it has been possible to increase the doxorubicin dose to that 
        given as a single agent and also maintain the ifosfamide dose. This is 
        now being tested in a randomized trial to determine whether improved 
        response rates and other indicators of outcome will be seen.

        Publication Types: 
          Clinical Trial 
          Multicenter Study 
          Review 
          Review, Tutorial 

        PMID: 1411615 [PubMed - indexed for MEDLINE] 




              7: Bull Acad Natl Med. 1991 Nov; 175(8): 1251-9; discussion 
              1259-60. Related Articles, Links 


        [Chemotherapy of soft tissue sarcoma in adults]

        [Article in French]

        Rouesse J, Spielmann M, Le Chevalier T, Tubiana-Hulin M, Tursz T.

        Centre Rene Huguenin, Saint-Cloud.

        The results of several studies of chemotherapy in treatment of soft 
        tissue sarcomas of adults (except embryonic rhabdomyosarcoma) are 
        presented. Most of these studies have been performed and published by 
        the EORTC Bone and Soft tissue sarcoma group. In advanced disease, a 
        randomized trial including 551 evaluable patients and comparing 
        doxorubicin alone (75 mg/m2 q. 3 weeks), and two combination regimens: 
        DI (Doxorubicin (50 mg/m2) + Ifosfamide (5 g/m2 + mesnum q. 3 weeks), 
        and Cyvadic (Doxorubicin 50 mg/m2 d1, DTIC 750 mg/m2 d1, VCR 1.5 mg/m2 
        d1 (maximum 2 mg/m2), Cyclophosphamide 500 mg/m2 d1 q. 3 weeks), failed 
        to prove any significant difference between these 3 treatments for 
        response rate (25%, 31%, 28%), quality of the response and survival. 
        There is a dose/effect relationship doxorubicin, it is possible that if 
        combination is not superior to a single agent, the reason could be that 
        the dose of doxorubicin is too low when used in combination as compared 
        with the dose when used alone. So, in a phase II trial including 48 
        evaluable patients, optimal dose of doxorubicin (75 mg/m2 and Ifosfamide 
        (5 g/m2) was given in association with rhGM-CSF. The response rate 
        observed with this combination was 50%. For localized disease, in a 
        randomized trial of the EORTC including 374 evaluable patients with 
        resectable tumors with a mean follow-up of 44 months, the interest of 8 
        Cyvadic as adjuvant chemotherapy after adequate locoregional treatment 
        (surgery with or without radiotherapy) was demonstrated only for 
        locoregional relapse free survival but no for metastatic disease free 
        survival or overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 1809496 [PubMed - indexed for MEDLINE] 




              8: J Surg Oncol. 1988 Aug; 38(4): 233-9. Related Articles, Links 


        Effect of adjuvant chemotherapy on time to recurrence and survival of 
        stage I uterine sarcomas.

        Piver MS, Lele SB, Marchetti DL, Emrich LJ.

        Department of Gynecologic Oncology, Roswell Park Memorial Institute, 
        Buffalo, New York 14263.

        We have evaluated the effect of adjuvant chemotherapy on time to 
        recurrence and survival in two prospective trials of women with stage I 
        uterine sarcomas. The first trial compared surgery only to surgery plus 
        Adriamycin. The 5-year estimated survival rate was 36% for surgery alone 
        and 63% for surgery plus Adriamycin. The 5-year recurrence free rate for 
        surgery alone was 46% as compared to 75% for surgery plus Adriamycin. 
        The second trial, without a concurrent control group, included patients 
        with stage I uterine sarcoma and adjuvant cyclaphosphamide, vincristine, 
        Adriamycin, and dacarbazine (CYVADIC) chemotherapy. The 5-year survival 
        rate was 89% and the recurrence-free rate was 80%. In all of these 
        trials, as well as in the report of Van Nagell et al (Cancer 
        57:1451-1454, 1986) of adjuvant vincristine, actinomycin-D, and 
        cyclophosphamide (VAC) chemotherapy, there are too few patients to make 
        any formal statistical comparison of the groups, although the surgery 
        plus CYVADIC group appears to be the most promising.

        Publication Types: 
          Clinical Trial 
          Controlled Clinical Trial 

        PMID: 3045423 [PubMed - indexed for MEDLINE] 




              9: Br J Cancer. 1985 Mar; 51(3): 301-18. Related Articles, Links 


        Combined modality management of local and disseminated adult soft tissue 
        sarcomas: a review of 257 cases seen over 10 years at the Christie 
        Hospital & Holt Radium Institute, Manchester.

        Bramwell VH, Crowther D, Deakin DP, Swindell R, Harris M.

        Over a 10 year period, between 1974-1984, 257 adult cases of tissue 
        sarcoma have been evaluated in the Department of Medical Oncology, 
        Christie Hospital, Manchester. At registration locally advanced or 
        metastatic diseases was present in 162 (63%). The male/female ratio was 
        1.5:1 and median age 54 years (range 14-85). The commonest sites were 
        lower limb (33%), visceral (21%), trunk (13%), retroperitoneum (12%) and 
        upper limb (10%). Leiomyosarcoma (27%), liposarcoma (14%) malignant 
        fibrous histiocytoma (10%) and neuro plus fibrosarcomas (15%) were the 
        most frequent histological subtypes. A high proportion of uterine 
        sarcomas (17%) is a point of distinction from many other series. 
        Histological grade was specified in 72% of cases and the distribution 
        (Grade I--27%; II--6%; III--67%) reflected a referral bias towards 
        advanced disease. Local resection of the primary tumour was performed in 
        76% of cases. In many instances this only amounted to 'shelling out' and 
        true compartmental excisions were rare. Amputation was performed in 31% 
        of patients with limb sarcomas. Ninety-eight patients (38%) had 
        experienced one or more local recurrences prior to referral and the 
        overall local recurrence rate was 56%. Suitable patients (78%) received 
        chemotherapy, 50% entering multicentre trials in collaboration with the 
        EORTC. The commonest regime used in patients with advanced disease was 
        CYVADIC which produced an overall response rate of 37%. Ifosfamide, used 
        as a single agent in 16 patients, induced 3CR and 5PR for an overall 
        response rate of 50%. When used in combination with MTX and VADIC, there 
        was no difference in response rate, but numbers in these pilot studies 
        were small. Seventeen high risk patients received adjuvant chemotherapy 
        with VAC, but the results (11 relapses) were disappointing. An EORTC 
        trial, comparing adjuvant CYVADIC chemotherapy with control has accrued 
        307 patients, 49 of these from the Christie Hospital. Preliminary 
        results within this centre - 13/25 relapses in the control arm, 5/23 in 
        the chemotherapy arm-suggest an advantage for chemotherapy but the data 
        are statistically not significant. Post-operative radical radiotherapy 
        after resection of the primary tumour or local recurrence was performed 
        in 51 patients, with local control in 65% of cases, although metastases 
        developed in 41%. At the time of analysis (1st April 1984) 98 (38%) were 
        alive, of whom 72 showed no evidence of disease and 52 had never 
        relapsed. Malignant disease was the cause of death in 92%. Overall 
        survival was not influenced by sex, but patients less than 40 years of 
        age fared significantly better (P less than 0.001).(ABSTRACT TRUNCATED 
        AT 400 WORDS)

        PMID: 3970810 [PubMed - indexed for MEDLINE] 




              10: Cancer. 1981 May 15; 47(10): 2422-9. Related Articles, Links 


        Protected environment - prophylactic antibiotic program for malignant 
        sarcomas: randomized trial during remission induction chemotherapy.

        Bodey GP, Rodriguez V, Murphy WK, Burgess A, Benjamin RS.

        Fifty-one valuable patients with malignant sarcomas were randomly 
        allocated to receive three courses of remission induction chemotherapy 
        with cyclophosphamide, vincristine, Adriamycin, and dimethyl triazeno 
        imidazole carboxamide (CYVADIC) on the protected 
        environment-prophylactic antibiotic for the control group (P = 0.22). 
        The response rates (complete plus partial) were 71% and 67%, 
        respectively. The durations of response were similar for both groups of 
        patients, but the PEPA patients survived substantially longer (median, 
        84 weeks vs. 58 weeks). The frequency of infection was significantly 
        lower among the PEPA patients, and the doses of CYVADIC could be 
        escalated more often among these patients. Dosage escalation was 
        associated with a higher complete remission rate and lower fatality 
rate.

        Publication Types: 
          Clinical Trial 
          Randomized Controlled Trial 

        PMID: 7272896 [PubMed - indexed for MEDLINE] 



              Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut 
              Related Articles Cited in Books Domain Links 3D Domain Links GEO 
              DataSet Links Gene Links Genome Links GEO Links Nucleotide Links 
              OMIM Links PMC Links Cited in PMC PopSet Links Protein Links SNP 
              Links Structure Links UniSTS Links UniSTS Links  Show: 5 10 20 50 
              100 200 500 Sort Author Journal Pub Date Text File Clipboard 
              E-mail Order 
                  Items 1-10 of 10One page.


         
         
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