Abstract
Adequate local treatment of soft tissue sarcomas has always been difficult in view of the local recurrence rate of 40 to 80% [1]. Most of these relapses occur within 3 years [2]. The use of sophisticated surgical techniques and the addition of postoperative high-dose radiotherapy have considerably reduced the number of local recurrences in extremity lesions [2–5]. Unfortunately, the inability to apply the required high doses of irradiation precluded a similar decrease in local recurrence in truncal lesions after surgery. Early hematogeneous spreading, most frequently to the lungs, is characteristic for soft tissue sarcomas and apparently can only in part be prevented by optimal local control of the primary tumor. Therefore, distant metastases still occur in a considerable number of patients for whom systemic treatment will be considered. This chapter summarizes the present achievements with systemic treatment of advanced soft tissue sarcomas.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Enneking WF, Spanier SS, Malawer MM: The effect of the anatomic setting on the results of surgical procedures for soft-part sarcomas of the thigh. Cancer 47:1005–1022, 1981.
Lindberg RD, Martin RG, Ramsdahl MM: Surgery and postoperative radiotherapy in the treatment of soft tissue sarcomas in adults. AJR Ther Nucl Med 123:123–129, 1975.
Gerson R, Shiu MH, Hajdu SI: Sarcoma of the buttock: A trend toward limb-salvage resection. J Surg Oncol 19:238–242, 1982.
Leibel SA, Tranbaugh RF, Wara WM, et al.: Soft tissue sarcomas of the extremities: Survival and patterns of failure with conservative surgery and postoperative irradiation compared to surgery alone. Cancer 50:1076–1083, 1982.
Suit HD, Mankin HJ, Wood WC, Proppe KH: Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma. Cancer 55:2659–2667,1985.
Bonadonna G, Beretta G, Tanchini G, et al.: Adriamycin (NSC-123127) studies at the Instituto Nazionale Tumori, Milan. Cancer Chemother Rep 6:231–245, 1975.
Verweij J, van Oosterom AT, Pinedo HM: Melanomas, soft tissue and bone sarcomas. Eur J Cancer Clin Oncol 4 (Suppl):75–85, 1985.
Borden EC, Amato DA, Rosenbaum Ch, et al.: Randomized comparison of three adria-mycin regiments for metastatic soft tissue sarcomas. J Clin Oncol 5:840–850, 1987.
Santoro A, Rouëssé J, Steward W, Mouridsen H, Verweij J, Somers R, Blackledge G, Buesa J, Sayer J, Casali P, Thomas D, Sylvester R: A randomized EORTC phase III study comparing adriamycin vs A plus ifosfamide vs CYVADIC in advanced soft tissue sarcoma. Proc ECCO 5:438, 1989.
Blackledge G, van Oosterom A, Mouridsen H, Steward WP, Buesa J, Thomas D, Sylvester R, Rouëssé J: Doxorubicin in relapsed soft tissue sarcoma: Justification of phase II evaluation of new drugs in this disease. An EORTC Soft Tissue and Bone Sarcoma Group study. Eur J Cancer Clin Oncol, in press.
O’Bryan RM, Luce JK, Talley RW: Phase II evaluation of adriamycin in human neo-plasma. Cancer 32:1–8, 1973.
Mitts DL, Gerhardt H, Armstrong D, et al.: Chemotherapy for advanced soft tissue sarcomas: Results of phase I and II cooperative studies. Tex Med 75:43–47, 1979.
Chlebowski RT, Paroly WS, Pugh RP: Adriamycin given as a weekly schedule without a loading course: Clinically effective with reduced incidence of cardiotoxicity. Cancer Treat Rep 64:49–51, 1980.
Benjamin RS, Yap BS: Infusion chemotherapy for soft tissue sarcomas. In: Soft tissue sarcomas. Baker LH (ed). Boston: Martinus Nijhoff, pp 109–116, 1983.
Samuels BL, Vogelzang NJ, Ruane M, Simon MA: Continuous venous infusion of doxorubicin in advanced sarcomas. Cancer Treat Rep 71:971–972, 1987.
Gerlach JH, Bell DR, Karakousis C, et al.: P-glycoprotein in human sarcoma: Evidence for multidrug resistance. J Clin Oncol 5:1452–1460, 1987.
Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D, Sylvester R: Adriamycin versus epirubicin in advanced soft tissue sarcomas: A randomized phase Il/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol 23:1477–1483, 1987.
Chevallier B, Monteuquet PH, Fachini T, Bui B, Tanguy A, Kerbrat P, Bastit PH, Hurteloup P: Phase II study of epirubicin in advanced soft tissue sarcoma. Proc Am Soc Clin Oncol 8:323, 1988.
Bodey GP, Yap BS, Ajani J: Clinical trials of 4’epidoxorubicin. Proc 13th Int Congr Chemother 215:23–26, 1983.
Bramwell VHC, Mouridsen HT, Mulder JH, Somers R, van Oosterom AT, Santoro A, Thomas D, Sylvester R, Markham D: Carminomycin vs adriamycin in advanced soft tissue sarcomas: An EORTC randomized phase II study. Eur J Cancer Clin Oncol 19:1097–1104, 1983.
Bertrand M, Multhauf P, Bartolucci A, Ellison D, Gockerman J: Phase II study of aclarubicin in previously untreated patients with advanced soft tissue sarcoma: A South-Eastern Cancer Study Group trial. Cancer Treat Rep 69:725–726, 1985.
Pazdur R, Samson MK, Baker LH: Aclacinomycin: Phase II evaluation in advanced soft tissue sarcoma. Am J Clin Oncol 10:237–239, 1987.
Raymond V, Magill GB, Wissel PS, Cheng WE, Ochoa M, Young CW: Phase II trial of deoxydoxorubicin in patients with soft tissue sarcoma. Proc Am Soc Clin Oncol 5:146, 1986.
Wissel PS, Magill GB, Raymond V, Well S, Sordillo P, Cheng E: 4′Demethoxydauno-rubicin in advanced soft tissue sarcomas: An update with emphasis on patients without prior doxorubicin. Proc Am Soc Clin Oncol 3:259, 1984.
Buckner JC, Edmonson JH, Ingle JN, Schaid DJ: Evaluation of menogaril in patients with metastatic sarcomas and no prior chemotherapy exposure. Am J Clin Oncol 12:384–386, 1989.
Presant CA, Gans R, Bartolucci AA: Treatment of metastatic sarcomas with mitoxantrone. Cancer Treat Rep 68:813–814, 1984.
Bull FE, von Hoff DD, Balcerzak SP, Stephens RL, Panetierre FJ: Phase II trial of mitoxantrone in advanced sarcomas: a South-West Oncology Group study. Cancer Treat Rep 69:231–233, 1985.
Gottlieb JA, Benjamin RS, Baker LH, et al.: Role of DTIC (NSC-45338) in the chemotherapy of sarcomas. Cancer Treat Rep 60:199–203, 1976.
Buesa J, Mouridsen H, van Oosterom AT, Steward WT, Verweij J, Thomas D: High-dose DTIC in advanced soft tissue sarcoma of the adult: A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Proc ECCO 4:235, 1987.
Hoefer-Janker H, Scheef W, Gunther U, et al.: Erfahrungen mit der fraktionierten Ifosfamid-Stoss Therapie bei generalisierten malignen Tumoren. Med Welt 26:972–979, 1977.
Klein HO, Wickramanayake PD, Coerper CL, et al.: High-dose ifosfamide and mesna as continuous infusion over five days: A phase I/II trial. Cancer Treat Rev 10:167–173, 1983.
Czownicki A, Utracka-Hutka B: Contribution to the treatment of malignant tumours with ifosfamide. In: Proceedings of the international Holoxan symposium. Burkert H, Voight HC (eds). Dusseldorf: ASTA-Werke, pp 109–111, 1977.
Antman KM, Montella D, Rosenbaum CH, Schwen M: Phase II trial of ifosfamide with mesna in previously treated metastatic sarcoma. Cancer Treat Rep 68:499–504, 1985.
Wiltshaw E, Westburg G, Harmer C, McKinna A, Fisher C: Ifosfamide plus mesna with and without adriamycin in soft tissue sarcoma. Cancer Chemother Pharmacol 18(Suppl 2):S10–12, 1986.
Bramwell VHC, Mouridsen H, Santoro A, Blackledge G, Somers R, Verweij J, Domber-nowsky P, Onsrud M, Thomas D, Sylvester R, van Oosterom AT: Cyclophosphamide versus ifosfamide: Final report of a randomized phase II trial in adult soft tissue sarcomas. Eur J Cancer Clin Oncol 23:311–321, 1987.
Legha S, Papadopoulos N, Usakewicz J, Fenoglio C, Nicaise C, Benjamin R: Role of ifosfamide in the treatment of refractory sarcomas and an evaluation of N-acetylcysteine as a uroprotector. Proc Am Soc Clin Oncol 9:322, 1989.
Quirt I, Eisenhauer E, Knowling M, Warr D, Bramwell V, Rusthoven J, Wierzbicki R, Verna S: A phase II study of Trimetrexate in metastatic soft tissue sarcoma. Proc Am Soc Clin Oncol 7:275, 1988.
Sordillo PP, Magill GB, Brenner J, Cheng EW, Dosik M, Yagoda A: A phase II evaluation of cisplatin in previously untreated patients with soft tissue sarcomas. Cancer 59:884–886, 1987.
Budd GT, Balcerzak S, Mortimer J, Fletcher W: SWOG 8465: High-dose cisplatin for advanced sarcomas. Proc Am Soc Clin Oncol 6:137, 1987.
Thigpen JT, Blessing JA, Wilbanks GD: Cisplatin as second-line chemotherapy in the treatment of advanced or recurrent leiomyosarcoma of the uterus: A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol (CCT) 9:18–20, 1986.
Sordillo PP, Magill GB, Welt S: Phase II trial of methylglyoxal-bis guanylhydrazone (methyl-GAG) in patients with soft-tissue sarcomas. Am J Clin Oncol (CCT) 8:316–318, 1985.
Thigpen JT, Blessing JA, Homesley HD, Hacker N, Curry SL: Phase II trial of piper-azinedione in patients with advanced or recurrent uterine sarcoma: A Gynecologic Oncology Group study. Am J Clin Oncol (CCT) 8:350–352, 1985.
Amato DA, Borden EC, Shiraki M, Enterline HT, Rosenbaum C, Davis HL, Paul AR, Stevens CM, Lerner HJ: Evaluation of bleomycin, chlorozotocin, MGBG, and bruceantin in patients with advanced soft tissue sarcoma, bone sarcoma, and mesothelioma. Invest New Drugs 3:397–401, 1985.
Chan C, Bartolucci A, Brenner D, Presant C, Davila E, Carpenter J, Greco A, Clamon G, Moore J: Phase II trial of diaziquone in anthracycline-resistant adult soft tissue and bone sarcoma patients: A South-Eastern Cancer Study Group trial. Cancer Treat Rep 70:427–428, 1986.
Cowan JD, Gehan E, Rivkin SE, Jones SE: Phase II trial of bisantrene in patients with advanced sarcoma: A South-West Oncology Group study. Cancer Treat Rep 70:685–686, 1986.
Wissel P, Magill G, Sordillo P, Cheng E, Hakes T, Applewhite A: A phase II trial of mitomycin C in advanced soft tissue sarcomas. Proc Am Soc Clin Oncol 5:146, 1986.
Ajani JA, Dimery I, Chawla SP, Pinnamaneni K, Benjamin RS, Legha S, Krakoff IH: Phase II studies of homoharringtonine in patients with advanced malignant melanomas, sarcoma, and head and neck, breast and colorectal carcinomas. Cancer Treat Rep 70:375–379, 1986.
Rouëssé JG, van Oosterom AT, Capellaere P, Kerbrat P, van Groeningen CJ, Thomas D, Benshahar D: Phase II study of 1,2,4-triglycidyl urasol (TGU) in advanced soft tissue sarcoma: A trial of the EORTC Soft Tissue and Bone Sarcoma Cooperative Group. Eur J Cancer Clin Oncol 23:1413–1414, 1987.
Dombernowsky P, Buesa J, Pinedo HM, Santoro A, Mouridsen HT, Somers R, Bramwell V, Onsrud M, Rouëssé J, Thomas D, Sylvester R: VP-16 in advanced soft tissue sarcoma: A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol 23:579–580, 1987.
Zalupski M, Pazdur R, Samson M, Baker L: Phase II clinical evaluation of fludarabine in soft tissue and osteosarcomas. Proc Am Soc Clin Oncol 6:135, 1987.
Pazdur R, Samson MK, Baker L: Fludarabine phosphate; Phase II evaluation in advanced soft tissue sarcomas. Am J Clin OnCol 10:341–343, 1987.
Blackledge G, Verweij J, Füchs R, Keizer J, Rodenhuis C, Rankin E, Kerbrat P, van Oosterom A, Sylvester R, Thomas D and Rouëssé J: A phase II study of M-azido-pyrimethamine ethane sulphonate (MZPES) in advanced recurrent soft tissue sarcoma: An EORTC Soft Tissue and Bone Sarcoma Group study. Eur J Cancer Clin Oncol, in press.
Steward WP, Mouridsen HT, Kerbrat P, Somers R, Verweij J, van Oosterom AT, Black-ledge G, Thomas D, Sylvester R: Phase II trial of methylene-dimethane sulphonate (MDMS) in advanced soft tissue sarcomas of the adult. Eur J Cancer Clin Oncol 25:1251-1253, 1989.
Thigpen JT, Blessing JA, Orr JW, DiSaia J: Phase II trial of cisplatin in the treatment of patients with advanced or recurrent mixed mesodermal sarcomas of the uterus: A gynecologic Oncology Group study. Cancer Treat Rep 70:271–271, 1986.
Gershenson DM, Kavanagh JJ, Copeland LJ, Edwardo CL, Stringer CA, Wharton JT: Cisplatin therapy for disseminated mixed mesodermal sarcoma of the uterus. J Clin Oncol 5:618–621, 1987.
Morrow CP, Bundy BN, Hoffman J, Sutton G, Homesley H: Adriamycin chemotherapy for malignant mixed mesodermal tumor of the uterus. Am J Clin Oncol (CCT) 9:24–26, 1986.
Gershenson DM, Kavanagh JJ, Copeland LJ, Edwards CL, Freedman RS, Wharton JT: High-dose doxorubicin infusion therapy for disseminated mixed mesodermal sarcoma of the uterus. Cancer 59:1264–1267, 1987.
Harris J, Das Gupta T, Vogelzang N, Badrinath K, Bonomi P, Desser R, Locker G, Blough R, Johnson C: Treatment of soft tissue sarcoma with fibroblast interferon (beta-interferon): An American Cancer Society/Illinois Cancer Council study. Cancer Treat Rep 70:293–294, 1986.
Edmonson JH, Long HJ, Creagan ET, Frytak S, Sherwin SA, Chang MN: Phase II study of recombinant gamma-interferon in patients with advanced non-osseous sarcomas. Cancer Treat Rep 71:211–213, 1987.
Salem P, Zikiwski A, Benjamin RS, Wallace S, Levitt D, Mavligit G: Arterial infusion of interleukin-2 for treatment of hepatic métastases from GI leiomyosarcoma: Predisposition to hypersensitivity to iodine-containing media. Proc Am Soc Clin Oncol 8:322, 1989.
Gottlieb JA, Baker LH, Quagliana JM, Luce JK, Whitecar JP, Sinkovics JG, Rivkin SE, Brownlee R, Frei E: Chemotherapy of sarcomas with a combination of adriamycin and dimethyl triazeno imidazole carboxamide. Cancer 30:1632–1638, 1972.
Omura GA, Major FJ, Blessing JA, Sedlacek TV, Thigpen JT, Creasman WT, Zaino RJ: A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 52:626–632, 1983.
Schoenfeld DA, Rosenbaum CH, Horton J, Wolter JM, Falkson G, De Conti RC: A comparison of adriamycin versus vincristine and adriamycin and cyclophosphamide versus vincristine, actinomycin-D and cyclosphosphamide for advanced sarcoma. Cancer 50:2757–2762, 1982.
Muss HB, Bundy B, DiSaia PJ, Homesley HD, Fowler WC, Creasman W, Yordan E: Treatment of recurrent or advanced uterine sarcoma: A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer 55:1648–1653, 1985.
Baker LH, Frank J, Fine G, Balcerak SP, Stephens RL, Stuckey WJ, Rivkin S, Saiki J, Ward JH: Combination chemotherapy using adriamycin, DTIC, cyclophosphamide and actinomycin-D for advanced soft tissue sarcomas: A randomized comparative trial — a phase III Southwest Oncology Group study (7613). J Clin Oncol 5:851–861, 1987.
Saiki JH, Baker LH, Rivkin SE, Shahbender S, Fletcher WS, Athens JW, Balcerak SP, Bonnet JD: A useful high-dose intermittent schedule of adriamycin and DTIC in the treatment of advanced sarcomas. Cancer 58:2196–2197, 1986.
Baker LH, Green S, Ryan J, Rosenberg B, Balcerak S: SWOG 8024: Combined modality therapy for disseminated soft tissue sarcoma, phase III. Proc Am Soc Clin Oncol 6:138, 1987.
Yap BS, Baker LH, Sinkovics JG, Rivkin SE, Bottomley R, Thigpen T, Burgess MA, Benjamin RS, Bodey GP: Cyclophosphamide, vincristine, adriamycin and DTIC (CYVADIC) combination chemotherapy for the treatment of advanced sarcomas. Cancer Treat Rep 64:93–98, 1980.
Yap BS, Burgess MA, Sinkovics JG, Benjamin RS, Bodey GP: A 5-year experience with cyclophosphamide, vincristine, adriamycin and DTIC (CYVADIC) chemotherapy in 169 adults with advanced soft tissue sarcoma. Proc Am Soc Clin Oncol 22:534, 1981.
Yap BS, Sinkovics JG, Burgess MA, Benjamin RS, Bodey GP: The curability of advanced soft tissue sarcomas in adults with chemotherapy. Proc Am Soc Clin Oncol 2:239, 1983.
Pinedo HM, Bramwell VHC, Mouridsen H, Somers R, Vendrik CPJ, Santoro A, Buesa J, Wagener TH, van Oosterom AT, van Unnik JAM, Sylvester R, de Pauw M, Thomas D, Bonadonna G: CYVADIC in advanced soft tissue sarcoma: A randomized study comparing two schedules. Cancer 53:1825–1832, 1984.
Karakousis CP, Rao U, Park HG: Combination chemotherapy (CYVADIC) in metastatic soft tissue sarcomas. Eur J Cancer Clin Oncol 18:33–36, 1982.
Kerzel W, Köning HJ, Walter M, Arnold I: Zytostatische Kombinationsbehandlung fortgeschrittener Sarkome: Ergebnisse einer prospektiv angelegten Studie. Tumor Diagn Ther 6:180–184, 1985.
Bui NB, Chauvergne J, Hocke C, Durand M, Brunet R, Coindre JM: Analysis of a series of sixty soft tissue sarcomas in adults treated with a cyclophosphamide-vincristine-adriamycin-dacarbazine (CYVADIC) combination. Cancer Chemother Pharmacol 15:82–85, 1985.
Schuette J, Mouridsen H, Santoro A, Steward W, van Oosterom AT, Somers R, Black-ledge G, Verweij J, Rouëssé J, Green JA, Pinedo HM, Kaye SB, Kerbrat H, Wagener T, Thomas D, Sylvester R: Adriamycin and ifosfamide, a new effective combination in advanced soft tissue sarcoma. Proc ECCO 4:232, 1987.
Cantwell BMJ, Carmichael J, Ghani S, Harris AL: A phase II study of ifosfamide/mesna with doxorubicin for adult soft tissue sarcoma. Cancer Chemother Pharmacol 21:49–52, 1988.
Loehrer PJ, Sledge GW, Nicaise C, Usakewicz J, Hainsworth JD, Martelo OJ, Omura G, Braun TJ: Ifosfamide plus doxuribicin in metastatic adult sarcomas: A multi-institutional phase II trial. J Clin Oncol 7:1655–1659, 1989.
Frustaci S, Foladore S, Lo Re G, Fosser V, Nascimben O, Tuveri G, Magri MD, Mon-fardini S: Full doses of ifosfamide and epirubicin in advanced soft tissue sarcomas. Proc Am Soc Clin Oncol 8:319, 1989.
Elias AD, Ryan L, Aisner J, Antman KH: Doxorubicin, ifosfamide and DTIC (AID) for advanced untreated sarcomas. Proc Am Soc Clin Oncol 6:134, 1987.
Bramwell V, Quirt I, Warr D, Verma S, Young V, Knowling M, Eisenhauer E: Combination chemotherapy with doxorubicin, dacarbazine and ifosfamide in advanced adult soft tissue sarcoma. J Natl Cancer Inst 81:1496–1499, 1989.
Klippstein TH, Mitrou PS, Kochendörfer KJ, Bergmann L: High dose adriamycin and cisplatinum in advanced soft tissue sarcomas and invasive thymomas: A pilot study. Cancer Chemother Pharmacol 13:78–81, 1984.
Hartlapp JH, Munch HJ, Illinger HJ, Wolter H, Jensen JC: Alternatives to CYVADIC combination therapy of soft tissue sarcomas. Cancer Chemother Pharmacol 18(Suppl 2): S20-S23, 1986.
Edmonson JH, Hahn RG, Schutt AJ, Bisel HF, Ingle JN: Cyclophosphamide, doxorubicin and cisplatin combined in the treatment of advanced sarcomas. Med Pediatr Oncol 11:319–321, 1983.
Piver MS, Lele SB, Patsner B: Cisdiamminedichloro-platinum plus dimethyl-triazenoi-midazole carboxamide as second-and third-line chemotherapy for sarcomas of the female pelvis. Gynecol Oncol 23:371–375, 1983.
Seltzer V, Kaplan B, Vogl S, Spitzer M: Doxorubicin and cisplatin in the treatment of advanced mixed mesodermal uterine sarcoma. Cancer Treat Rep 68:1389–1390, 1984.
Moore N, Fine S, Sturgeon J: Malignant mixed mesodermal tumors of the ovary: The Princess Margaret Hospital experience. Proc Am Soc Clin Oncol 5:114, 1986.
Jansen RLH, van der Burg MEL, Verweij J, Stoter G: Cyclophosphamide, hexamethylme-lamine, adriamycin and cisplatin combination chemotherapy in mixed mesodermal sarcoma of the female genital tract. Eur J Cancer Clin Oncol 23:1131–1133, 1987.
Rouëssé JG, Friedman S, Sevin DM, Le Chevalier TH, Spielmann ML, Contesso G, Sarrazin DM, Genin JR: Preoperative induction chemotherapy in the treatment of locally advanced soft tissue sarcomas. Cancer 60:296–300, 1987.
Lagarde C, Bui NB, Marée D, Coindre JP, Kantor G, Bussières E: Locally advanced soft tissue sarcomas. Preliminary results of a multi-disciplinary approach with initial (neo-adjuvant) chemotherapy in a series of 46 patients. Proc Am Soc Clin Oncol 7:274, 1988.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media New York
About this chapter
Cite this chapter
Verweij, J., Pinedo, H.M. (1991). Systemic Treatment of Advanced or Metastatic Soft Tissue Sarcomas. In: Pinedo, H.M., Verweij, J., Suit, H.D. (eds) Soft Tissue Sarcomas: New Developments in the Multidisciplinary Approach to Treatment. Cancer Treatment and Research, vol 56. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3896-7_7
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3896-7_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6738-3
Online ISBN: 978-1-4615-3896-7
eBook Packages: Springer Book Archive