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Combination chemotherapy for patients with recurrent or advanced uterine sarcomas
254
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
This is a report of six patients with endodermal sinus tumor of the vagina and cervix, a polypoid friable tumor whose clinical presentation in girls under age 3 simulates that of sarcoma botryoides. In four of the six patients, the referring diagnosis was sarcoma botryoides. Five patients were treated with excisional surgery, and all six with chemotherapy. One patient with pulmonary metastases maintained a complete clinical response to vincristine, actinomycin D, and cyclophosphamide (VAC) for 11 months. One patient with a vaginal lesion remains clinically free of disease 2 years after local excision and 18 months of VAC chemotherapy. This illustrates the possibility of retaining reproductive capacity in some of these patients. Four of the six patients have been disease-free from 2 to 23 years. The authors conclude that a combination of chemotherapy and surgery offers a reasonable prospect of cure with a minimum of serious side effects. 19. Combination Chemotherapy for Patients with Recurrent or Advanced Uterine Sarcomas. J. CURRIE,T. SWIGER,M. DUDZINSKI,L. WALTON,AND W. FOWLER,University of North Carolina, Chapel Hill, North Carolina 27514. Two combination-chemotherapy regimens, high-dose methotrexate with folinic acid rescue, Adriamycin, Cytoxan, and vincristine (Hi-Mac-V), and hydroxyurea, DTIC, and VP-16, (VPHD) were used to treat 13 patients with recurrent or advanced uterine sarcomas. Seven patients had mixed mullerian tumors, two patients suffered stromal sarcomas, and four had leiomyosarcomas, with ages ranging from 40 to 73 years. Nine patients had undergone prior single-agent or combination chemotherapy for 4-18 courses. In general, toxicity was acceptable. Of 7 patients treated with Hi-Mac-V, 1 exhibited complete response lasting 4 months, I had partial response lasting six months, and 2 exhibited progressive disease; all 4 were subsequently treated with VPHD. Three patients are currently being treated with Hi-Mac-V, one of whom exhibited progression after stable disease for 8 months. Two patients have had partial responses of 2 and 12 months and are still undergoing therapy. Ten patients have been treated with VPHD, 6 of whom were treated with this regimen without prior Hi-Mac-V. Overall, there have been 5 patients with complete responses of 17-24 months, 2 of whom suffered relapses. Two patients received one course each of VPHD but died without additional treatment. One patient had stable disease for 3 months before suffering progressive disease. Two patients had no response. Of 12 evaluable patients, 10 have achieved favorable responses to either one or both intensive chemotherapy regimens, with 5 patients exhibiting sustained complete responses of 17 to 24 months. 20. Mullerian-Inhibiting Substance as a Cancer Therupeutic Agent. ARLAN F. FULLER,JR., M.D., IAN M. KRANE, GERALDBUKZIK, PH.D., ANDPATRICIAK. DONAHOE,M.D., Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114. Mullerian-inhibiting substance (MIS) is the product of the fetal sertoli cell that causes regression of the Mullerian duct in the male mammalian embryo. With the hypothesis that a drug active against the precursor of the female genital tract in the fetus might also be active against tumors derived from these tissues, we previously demonstrated its anticancer effect against two cell lines derived from cervical and ovarian adenocarcinomas in vitro. We have similarly demonstrated prevention of tumor heterotransplantation into nude mice when established ovarian and endometrial carcinoma lines were treated with MIS prior to inoculation. We have now investigated the effect of increasingly purified MIS preparations in the inhibition of colony growth of 28, fresh human gynecologic cancers. Increased antitumor response followed increased purification of MIS from 7- to 8000-fold compared with the original incubation medium. These experiments support our contention that mullerianinhibiting substance is the active principle producing this antitumor effect. 21. Analysis of Clinical Trials in Gynecologic Cancer-Timing and Interpretation. J. BLESSINGAND B. ANDERSON,Gynecologic Oncology Group Statistical Office, Buffalo, New York 14263 and University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242. When and how often a clinical trial is analyzed is as important as the use of appropriate methodology. Premature analysis may underestimate response, overestimate adverse effects, and misrepresent survival. Moreover, bias may be introduced or the study may be abandoned entirely. Repeated
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
This is a report of six patients with endodermal sinus tumor of the vagina and cervix, a polypoid friable tumor whose clinical presentation in girls under age 3 simulates that of sarcoma botryoides. In four of the six patients, the referring diagnosis was sarcoma botryoides. Five patients were treated with excisional surgery, and all six with chemotherapy. One patient with pulmonary metastases maintained a complete clinical response to vincristine, actinomycin D, and cyclophosphamide (VAC) for 11 months. One patient with a vaginal lesion remains clinically free of disease 2 years after local excision and 18 months of VAC chemotherapy. This illustrates the possibility of retaining reproductive capacity in some of these patients. Four of the six patients have been disease-free from 2 to 23 years. The authors conclude that a combination of chemotherapy and surgery offers a reasonable prospect of cure with a minimum of serious side effects. 19. Combination Chemotherapy for Patients with Recurrent or Advanced Uterine Sarcomas. J. CURRIE,T. SWIGER,M. DUDZINSKI,L. WALTON,AND W. FOWLER,University of North Carolina, Chapel Hill, North Carolina 27514. Two combination-chemotherapy regimens, high-dose methotrexate with folinic acid rescue, Adriamycin, Cytoxan, and vincristine (Hi-Mac-V), and hydroxyurea, DTIC, and VP-16, (VPHD) were used to treat 13 patients with recurrent or advanced uterine sarcomas. Seven patients had mixed mullerian tumors, two patients suffered stromal sarcomas, and four had leiomyosarcomas, with ages ranging from 40 to 73 years. Nine patients had undergone prior single-agent or combination chemotherapy for 4-18 courses. In general, toxicity was acceptable. Of 7 patients treated with Hi-Mac-V, 1 exhibited complete response lasting 4 months, I had partial response lasting six months, and 2 exhibited progressive disease; all 4 were subsequently treated with VPHD. Three patients are currently being treated with Hi-Mac-V, one of whom exhibited progression after stable disease for 8 months. Two patients have had partial responses of 2 and 12 months and are still undergoing therapy. Ten patients have been treated with VPHD, 6 of whom were treated with this regimen without prior Hi-Mac-V. Overall, there have been 5 patients with complete responses of 17-24 months, 2 of whom suffered relapses. Two patients received one course each of VPHD but died without additional treatment. One patient had stable disease for 3 months before suffering progressive disease. Two patients had no response. Of 12 evaluable patients, 10 have achieved favorable responses to either one or both intensive chemotherapy regimens, with 5 patients exhibiting sustained complete responses of 17 to 24 months. 20. Mullerian-Inhibiting Substance as a Cancer Therupeutic Agent. ARLAN F. FULLER,JR., M.D., IAN M. KRANE, GERALDBUKZIK, PH.D., ANDPATRICIAK. DONAHOE,M.D., Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114. Mullerian-inhibiting substance (MIS) is the product of the fetal sertoli cell that causes regression of the Mullerian duct in the male mammalian embryo. With the hypothesis that a drug active against the precursor of the female genital tract in the fetus might also be active against tumors derived from these tissues, we previously demonstrated its anticancer effect against two cell lines derived from cervical and ovarian adenocarcinomas in vitro. We have similarly demonstrated prevention of tumor heterotransplantation into nude mice when established ovarian and endometrial carcinoma lines were treated with MIS prior to inoculation. We have now investigated the effect of increasingly purified MIS preparations in the inhibition of colony growth of 28, fresh human gynecologic cancers. Increased antitumor response followed increased purification of MIS from 7- to 8000-fold compared with the original incubation medium. These experiments support our contention that mullerianinhibiting substance is the active principle producing this antitumor effect. 21. Analysis of Clinical Trials in Gynecologic Cancer-Timing and Interpretation. J. BLESSINGAND B. ANDERSON,Gynecologic Oncology Group Statistical Office, Buffalo, New York 14263 and University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242. When and how often a clinical trial is analyzed is as important as the use of appropriate methodology. Premature analysis may underestimate response, overestimate adverse effects, and misrepresent survival. Moreover, bias may be introduced or the study may be abandoned entirely. Repeated