- Email: [email protected]
Endometrial stromal sarcoma: A gynecologic oncology group clinico-pathologic study of 46 cases
188
SOCIETY OF GYNECOLOGISTS
recurred and 100 mm’ in those who are disease free (P > 0.10). Recurrence was influenced by depth. Median depth was 0.9 mm in those who remained disease free and 4.68 mm in those who suffered recurrence (P < 0.01). None of the pts with less than 2 mm depth recurred whereas 100% of those with a depth greater than 2 mm recurred (P = 0.0004). The 4 pts treated with WLE had a median blood loss of 100 cc (range 30-200), whereas the 12 pts treated with RVLND or RV had a median blood loss of 750 cc (range 200-1500) (P < 0.01). Median hospital stay was 4 days (range O-13) in those who received a WLE versus 24.5 days (range 8-43) in those who had radical surgery (P = 0.01). Three of four patients (75%) with WLE remain disease free versus 4/12 (33%) of those treated with RV or RVLND. Those pts with MMV with a depth less than 2 mm should receive a WLE. RVLND may not benefit those pts with lesions greater than 2 mm in depth. Since pts had a median survival time of 5.9 months (range 2-21) after recurrence, a less aggressive surgical approach may be justified. 86. The Analysis of the Ability of TNFa to Induce Resistance to TNFa in Malignant Gynecologic Cell Lines. C. B. POWELL, D. G. MUTCH,
M-S. KAO, AND J. L. COLLINS, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes Hospital Plaza, St. Louis, Missouri 63110. Tumor necrosis factor (Y (TNFa) mediates a variety of biological responses, included among these is the potential to lyse tumore cells in vitro. In addition to activating a lytic mechanism TNFL~has also been shown to induce a resistance mechanism in some cells that prevents them from being lysed by TNFLu. This seemingly paradoxical finding could obviously impact on the use of TNFo as an anticancer agent. We have previously shown that TNFa induces a lytic mechanism in a number of cell lines derived from gynecologic malignancies. Because these cell lines constitutively express a protein synthesis-dependent TNFcv resistance mechanism, the induction of the lytic mechanism can only be revealed when protein synthesis is inhibited. In order to determine if, in addition to the constitutively expressed resistance mechanism, TNFa is also capable of inducing a resistance mechanism in these cells, cells were first pretreated with TNFa before lysis by TNFa was measured in the presence of protein synthesis inhibitors. The results of this analysis showed that TNFa induced significant levels of resistance to lysis by TNFo (P < 0.01) in the cervical carcinoma cell line SiHa. TNFa did not induce resistance in the cervical carcinoma cell line ME-180, nor did it induce resistance in either of the ovarian carcinoma cell lines OVCAR3 or SK-OV-3. In addition to the requirement for induction, the resistance mechanism induced by TNFo in SiHa cells is distinct from the constitutive resistance mechanism expressed by this cell line in that the induced resistance is not dependent on the maintenance of protein synthesis. The fact that TNFa does induce resistance to itself in SiHa cells could, in part, explain why some cancers are refractory to treatment with TNFa. We would predict that these cancers would remain refractory to treatment with TNFo even in the presence of protein synthesis inhibitors. 87. Interferon a (IFNo): Induction of a Lytic Mechanism in Malignant Gynecologic Cell Lines. C. B. POWELL, D. G. MUTCH, M-S. KAO, AND J. L. COLLINS, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes Hospital Plaza, St. Louis, Missouri 63110.
Although interferon (Y (IFNo) has been shown to have in vitro antiproliferative activity in many cancer cell lines, there have been no reports of its cytolytic activity. This may, in part, explain why most gynecologic tumors have had poor in vivo responses to IFNa. We now report that IFNa induces a lytic mechanism in six of six randomly selected malignant gynecologic cell lines. Because the lytic mechanism is opposed by a protein synthesis-dependent resistance mechanism, lysis only occurs when protein synthesis is blocked. Neither the cervical (C-
ONCOLOGISTS-ABSTRACTS 33A, ME-180, SiHa, MS751) nor the ovarian (SK-OV-3, Caov-3) carcinoma cell lines were lysed by IFNa alone or in combination with protein synthesis inhibitors. However, significant lysis occurred in all cell lines when they were pretreated for 24 hr with IFNa before protein synthesis was inhibited. In the Table below, the increased lysis by IFNo pretreatment is compared to the baseline lysis by protein synthesis inhibitors in the absence of IFNa pretreatment. Percentage Increase in Lysis by IFNo Pretreatment
Cell line SiHa ME-180 MS751 C-33A SK-OV3 Caov-3
1000 IU/ml
10,000 IU/ml
100,000 IU/ml
230 (NS) 700 (P
630 (PcO.05) 1030 (P
1270 (P
Because lysis occurs only after pretreatment, the lytic mechanism must require induction. Further, the fact that lysis only occurs under conditions in which protein synthesis is blocked indicates that there is a resistance mechanism which prevents lysis by IFNo. Eliminating this resistance may be the key to overcoming the disappointing results with IFNa as an anticancer agent. Since we have previously shown that there is a protein synthesis-dependent resistance mechanism that prevents lysis by TNFa and INFy, the results presented here lend further support for a common mechanism that may prevent lysis by a variety of biological response modifiers. 88. Cervical lntraepithelial
Neoplasia (GIN) following
Cryotherapy
Fail-
ure. P. P. KOONINGS, G. D’ABLAING, J. B. SCHLAERTH, C. P. MORROW, AND J. P. CURTIN, Women’s Hospital, Los Angeles, California
90033. From 1979 through 1988 27 patients underwent cone biopsy for presumed CIN subsequent to cryotherapy. Prior to cryotherapy, 4 patients had a cervical biopsy consistent with CIN I (15%), 6 patients had CIN II (22%), and 17 patients had CIN III (63%). All patients had satisfactory colposcopic examinations and a negative ECC. A single freeze method of cryotherapy was then performed. The indications for cone biopsy in these patients were an unsatisfactory colposcopic examination or a positive endocervical curettage. Cervical biopsy confirmed all treatment failures. The grade of the CIN in the postcryotherapy biopsy remained constant in 16 patients (59%), increased in 7 patients (26%), and decreased in 6 patients (22%). In 9 patients the cone biopsy showed the same degree of dysplasia as the precryotherapy biopsy (33%) while in 9 patients (33%) it had worsened, and in 9 patients (33%) it had improved. Similarly when the postcryotherapy biopsy was compared to the cone biopsy, the degree of dysplasia had improved in 7 patients (26%), worsened in 8 patients (30%), and remained constant in 12 patients (44%). Invasive squamous cell carcinoma was found in 3 patients (11%). Patients presenting with recurrent CIN after cryotherapy can have progressive disease and should be managed aggressively. 89. Endometrial Stromal Sarcoma: A Gynecologic Oncology Group Clinico-Pathologic Study of 46 Cases. T. KAKU, S. G. SILVERBERG, F. J. MAJOR, A. MILLER, B. FETTER, AND J. A. BLESSING, Gynecologic Oncology Group Headquarters, Philadelphia, Pennsylvania 19107.
Forty-six patients with clinical stage I or II endometrial stromal sarcoma (ESS) underwent hysterectomy and staging laparotomy in order to define the criteria for dividing these tumors into those at low and high risk for extrauterine spread, recurrence, and death. Cases were classified as low grade (LG, 20 cases), high grade (HG, 21) or undifferentiated (W, 5). Although LG cases were more frequently upstaged
SOCIETY
OF GYNECOLOGISTS
at laparotomy (50% vs 33% of Hg and 20% of U), and lymph node metastasis rates were equal (14-20%), LG cases had lower short-term recurrence (10% vs S&60%) and death (0 vs 45-60%) rates than HG/U. LG-ESS also occurred in younger patients and differed from HG/U cases in showing less mitotic activity, atypical mitoses, and tumor necrosis. HG/U cases can be combined for practical purposes, but must be separated from LG-ESS. 90. A New in Vitro Radiation Sensitivity Assay Based on ATP-Bioluminescence and Cell Cycle Perturbations Detected by Flow Cytometry. G. BOIKE, H. AvmwrE. C. Gom.m, AND R. RAMOS, University of Miami, Miami, Florida 33101. Historically, there has been tremendous interest in methods to predict tumor radiosensitivity and curability. Recent efforts have concentrated on various short-term in vitro sensitivity assays and flow cytometric measurements of proliferation kinetics and ploidy. The purpose of our study was to evaluate the correlation between radiation-induced cytotoxicity determined with the ATP-bioluminescence assay (Gynecol. Uncol. 31, IYl. 1988) and cell cycle perturbations detected with dualparameter flow cytometry (Gynecol. Oncol. 32,282. 1988). Two cervical squamous cell carcinoma lines (ME-180 and SiHa) and one ovarian adenocarcinoma cell line (CaOv-3) were studied. All lines demonstrated radiation dose-dependent survival curves. The radiation doses for 50% inhibition of control ATP values (IC50) were: 3.56 Gray (Gy), 6.61 Gy, and 3.38 Gy for ME-IHO, SiHa, and CaOv-3. respectively. The magnitude of accumulation in the G2 phase of the cell cycle, maximal 24-48 hr after irradiation, was dose dependent in all cell lines studied. In the squamous cell lines there was good correlation between the radiosensitivity (ICSO) and the magnitude of G2 accumulation 24 or 48 hr after irradiation. The concurrent use of these two in vitro modalities may prove clinically useful in prospectively assessing tumor radiosensitivity and curability. 01. Phase II Trial of lfosfamide and Mesna in Chemotherapy-Naive Patients with Recurrent or Advanced Squamous Carcinoma of the Cervix. G. SUI.I.ON. J. BINSSING, W. MCGUIRE, AND T. PATTON, the Gynecologic Oncology Group (GOG). Philadelphia, Pennsylvania 19 107. A phase II trial of ifosfamide (IFX) and mesna was conducted by the GOG in patients with recurrent or advanced squamous carcinoma of the cervix who had not received prior chemotherapy. A starting dose of 1.5 g/m’ IFX iv daily for 5 days and 300 mg/m’ mesna iv q 4 hr times three doses daily after IFX were given. In patients who had received prior radiotherapy, the starting dose of IFX was reduced to I.2 g/m’. Fifty-six patients were entered. Two patients each are ineligible and inevaluable and five are too early. Forty-seven are evaluable for toxicity and 46 for response. Age range was 20-84 years. GOG performance status was O-1 for all but nine patients. Forty-one patients had prior radiotherapy. Seven patients (14.‘)) developed GOG grade 3 or 4 granulocytopcnia and two developed grade 3 thrombocytopenia. There were one complete and six partial responses (15.2%) and 25 patients (54.4%) with stable disease for at least 3 months on therapy. Although ifosfamide has activity in this group of chemotherapy-naive patients with squamous carcinoma of the cervix, the dose schedule utilized in this study fails to confirm the high response rate reported by other investigators. 92. Laser Skinning Vulvectomy for Vulvar Intraepithelial Neoplasia. T. SEDLACEK, AND W. BRADFORD, Pennsylvania Hospital, Philadelphia. Pennsylvania 19107. A retrospective review of vulvar intraepithelial neoplasia (VIN) treated by excision skinning vulvectomy was conducted. Thirty-nine patients underwent primary therapy for VIN by laser skinning vulvectomy between l/83 and 12/8Y. All patients underwent colposcopy and
ONCOLOGISTS-ABSTRACTS
189
biopsy 3 months after surgery; 1 patient was lost to follow up. Median follow up was 2 years. Recurrence was noted in 5 patients (12.8%). Previous lower genital tract treatment for human papilloma virus (HPV) or intraepithelial neoplasia was noted in 27 patients (70%). Positive resection margins were noted in 7 patients (18%); 6 of whom were disease free on subsequent colposcopy. No patients had invasive cancer in the vulvectomy specimen. Twenty-nine patients had a history of genital warts or positive HPV typing. Eleven of these 29 patients were HPV positive on dot blot (8 16/18, 2 31,33.35, 1 6/11). Cigarette smoking was reported in 22 of 35 patients who responded. Patients who recurred did not differ from patients treated successfully in age of coitarche. cigarette use, other sexually transmitted diseases, number of sexual partners, or HPV type, Excision skinning vulvectomy is an effective treatment modality for VIN and allows for histologic review of the surgical specimen. Y3. CAI25-A Potential Prognostic Indicator in Patients with Cervical Carcinoma? G. L. GOLDBERG, A. SKL.AR. A. ASHER, P. A. LEVINE, K. A. O’HANLAN, AND C. D. RUNOWICZ, Albert Einstein College of Medicine, Bronx, New York 10461. Despite widespread screening. invasive cervical cancer (CxCa) remains a significant problem in the U.S. Irrespective of the clinical stage or the treatment modality, monitoring of the actual disease status is difficult and unreliable. CA125 has been shown to be useful in the follow-up of patients (pts) with ovarian and endometrial carcinomas. We performed a retrospective analysis on 104 patients with CxCa. Preand post-therapy CA125 levels were available in 64 pts. At initial presentation 19 pts (30%) had levels >35 U/ml, 12 pts (19%) had levels 16-35 U/ml, and 33 pts (51%) had levels ~16 U/ml. Eleven pts had pre- and post-treatment levels >35 U/ml. Ten of these II pts died of disease and 1 pt is alive with persistent or recurrent disease. Of the 20 pts with elevated levels at presentation that reverted to normal after therapy, IY are clinically free of disease at 14-46 months (median 27 months). Of the 33 pts with normal pre- and post-therapy CA125 levels, 31 pts are clinically without evidence of disease. Two pts had increasing CA125 levels at follow-up, and both had disease recurrence. One is dead of disease at 7 months and 1 is alive with disease at 8 months. There was no correlation between the CA125 level and the tumor type, grade. or stage of disease. Our data suggest that pts with initially elevated CA125 levels that revert to normal after therapy have a favorable prognosis. Persistent elevation of the CA125 levels during and after therapy in pts with CxCa was associated with a poor prognosis. 94. Phase II Trial of High Dose Cisplatin (C) with Sodium Thiosulfate (STS) Protection in Patients with Advanced Carcinoma of the Cervix (ACC) Previously Untreated with Chemotherapy. B. REICHMAN, M. MARKMAN. T. HAKES, W. JONES, S. RUBIN, W. HOSKINS, AND J. L. LEWIS. JR.. Memorial Sloan-Kettering Cancer Center, New York, New York 10021. C is one of the most active single agents in the treatment of ACC. A previously reported Phase I trial showed that the dose of C could be significantly increased with the simultaneous administration of STS and also suggested enhanced activity in ACC (Proc. Asco. 7,55, 1988). On this basis the current trial was instituted to explore the role of dose intensity in ACC. C was given iv at 200 mg/m’ as a 2H infusion with iv STS at 3.3 mg/m’ 1 hr prior to C, and 6.6 mg/m’ during C infusion. Standard antiemetics and hydration of at least 2 liters of saline were given. Treatment was repeated monthly. Patients who had
SOCIETY OF GYNECOLOGISTS
recurred and 100 mm’ in those who are disease free (P > 0.10). Recurrence was influenced by depth. Median depth was 0.9 mm in those who remained disease free and 4.68 mm in those who suffered recurrence (P < 0.01). None of the pts with less than 2 mm depth recurred whereas 100% of those with a depth greater than 2 mm recurred (P = 0.0004). The 4 pts treated with WLE had a median blood loss of 100 cc (range 30-200), whereas the 12 pts treated with RVLND or RV had a median blood loss of 750 cc (range 200-1500) (P < 0.01). Median hospital stay was 4 days (range O-13) in those who received a WLE versus 24.5 days (range 8-43) in those who had radical surgery (P = 0.01). Three of four patients (75%) with WLE remain disease free versus 4/12 (33%) of those treated with RV or RVLND. Those pts with MMV with a depth less than 2 mm should receive a WLE. RVLND may not benefit those pts with lesions greater than 2 mm in depth. Since pts had a median survival time of 5.9 months (range 2-21) after recurrence, a less aggressive surgical approach may be justified. 86. The Analysis of the Ability of TNFa to Induce Resistance to TNFa in Malignant Gynecologic Cell Lines. C. B. POWELL, D. G. MUTCH,
M-S. KAO, AND J. L. COLLINS, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes Hospital Plaza, St. Louis, Missouri 63110. Tumor necrosis factor (Y (TNFa) mediates a variety of biological responses, included among these is the potential to lyse tumore cells in vitro. In addition to activating a lytic mechanism TNFL~has also been shown to induce a resistance mechanism in some cells that prevents them from being lysed by TNFLu. This seemingly paradoxical finding could obviously impact on the use of TNFo as an anticancer agent. We have previously shown that TNFa induces a lytic mechanism in a number of cell lines derived from gynecologic malignancies. Because these cell lines constitutively express a protein synthesis-dependent TNFcv resistance mechanism, the induction of the lytic mechanism can only be revealed when protein synthesis is inhibited. In order to determine if, in addition to the constitutively expressed resistance mechanism, TNFa is also capable of inducing a resistance mechanism in these cells, cells were first pretreated with TNFa before lysis by TNFa was measured in the presence of protein synthesis inhibitors. The results of this analysis showed that TNFa induced significant levels of resistance to lysis by TNFo (P < 0.01) in the cervical carcinoma cell line SiHa. TNFa did not induce resistance in the cervical carcinoma cell line ME-180, nor did it induce resistance in either of the ovarian carcinoma cell lines OVCAR3 or SK-OV-3. In addition to the requirement for induction, the resistance mechanism induced by TNFo in SiHa cells is distinct from the constitutive resistance mechanism expressed by this cell line in that the induced resistance is not dependent on the maintenance of protein synthesis. The fact that TNFa does induce resistance to itself in SiHa cells could, in part, explain why some cancers are refractory to treatment with TNFa. We would predict that these cancers would remain refractory to treatment with TNFo even in the presence of protein synthesis inhibitors. 87. Interferon a (IFNo): Induction of a Lytic Mechanism in Malignant Gynecologic Cell Lines. C. B. POWELL, D. G. MUTCH, M-S. KAO, AND J. L. COLLINS, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes Hospital Plaza, St. Louis, Missouri 63110.
Although interferon (Y (IFNo) has been shown to have in vitro antiproliferative activity in many cancer cell lines, there have been no reports of its cytolytic activity. This may, in part, explain why most gynecologic tumors have had poor in vivo responses to IFNa. We now report that IFNa induces a lytic mechanism in six of six randomly selected malignant gynecologic cell lines. Because the lytic mechanism is opposed by a protein synthesis-dependent resistance mechanism, lysis only occurs when protein synthesis is blocked. Neither the cervical (C-
ONCOLOGISTS-ABSTRACTS 33A, ME-180, SiHa, MS751) nor the ovarian (SK-OV-3, Caov-3) carcinoma cell lines were lysed by IFNa alone or in combination with protein synthesis inhibitors. However, significant lysis occurred in all cell lines when they were pretreated for 24 hr with IFNa before protein synthesis was inhibited. In the Table below, the increased lysis by IFNo pretreatment is compared to the baseline lysis by protein synthesis inhibitors in the absence of IFNa pretreatment. Percentage Increase in Lysis by IFNo Pretreatment
Cell line SiHa ME-180 MS751 C-33A SK-OV3 Caov-3
1000 IU/ml
10,000 IU/ml
100,000 IU/ml
230 (NS) 700 (P
630 (PcO.05) 1030 (P
1270 (P
Because lysis occurs only after pretreatment, the lytic mechanism must require induction. Further, the fact that lysis only occurs under conditions in which protein synthesis is blocked indicates that there is a resistance mechanism which prevents lysis by IFNo. Eliminating this resistance may be the key to overcoming the disappointing results with IFNa as an anticancer agent. Since we have previously shown that there is a protein synthesis-dependent resistance mechanism that prevents lysis by TNFa and INFy, the results presented here lend further support for a common mechanism that may prevent lysis by a variety of biological response modifiers. 88. Cervical lntraepithelial
Neoplasia (GIN) following
Cryotherapy
Fail-
ure. P. P. KOONINGS, G. D’ABLAING, J. B. SCHLAERTH, C. P. MORROW, AND J. P. CURTIN, Women’s Hospital, Los Angeles, California
90033. From 1979 through 1988 27 patients underwent cone biopsy for presumed CIN subsequent to cryotherapy. Prior to cryotherapy, 4 patients had a cervical biopsy consistent with CIN I (15%), 6 patients had CIN II (22%), and 17 patients had CIN III (63%). All patients had satisfactory colposcopic examinations and a negative ECC. A single freeze method of cryotherapy was then performed. The indications for cone biopsy in these patients were an unsatisfactory colposcopic examination or a positive endocervical curettage. Cervical biopsy confirmed all treatment failures. The grade of the CIN in the postcryotherapy biopsy remained constant in 16 patients (59%), increased in 7 patients (26%), and decreased in 6 patients (22%). In 9 patients the cone biopsy showed the same degree of dysplasia as the precryotherapy biopsy (33%) while in 9 patients (33%) it had worsened, and in 9 patients (33%) it had improved. Similarly when the postcryotherapy biopsy was compared to the cone biopsy, the degree of dysplasia had improved in 7 patients (26%), worsened in 8 patients (30%), and remained constant in 12 patients (44%). Invasive squamous cell carcinoma was found in 3 patients (11%). Patients presenting with recurrent CIN after cryotherapy can have progressive disease and should be managed aggressively. 89. Endometrial Stromal Sarcoma: A Gynecologic Oncology Group Clinico-Pathologic Study of 46 Cases. T. KAKU, S. G. SILVERBERG, F. J. MAJOR, A. MILLER, B. FETTER, AND J. A. BLESSING, Gynecologic Oncology Group Headquarters, Philadelphia, Pennsylvania 19107.
Forty-six patients with clinical stage I or II endometrial stromal sarcoma (ESS) underwent hysterectomy and staging laparotomy in order to define the criteria for dividing these tumors into those at low and high risk for extrauterine spread, recurrence, and death. Cases were classified as low grade (LG, 20 cases), high grade (HG, 21) or undifferentiated (W, 5). Although LG cases were more frequently upstaged
SOCIETY
OF GYNECOLOGISTS
at laparotomy (50% vs 33% of Hg and 20% of U), and lymph node metastasis rates were equal (14-20%), LG cases had lower short-term recurrence (10% vs S&60%) and death (0 vs 45-60%) rates than HG/U. LG-ESS also occurred in younger patients and differed from HG/U cases in showing less mitotic activity, atypical mitoses, and tumor necrosis. HG/U cases can be combined for practical purposes, but must be separated from LG-ESS. 90. A New in Vitro Radiation Sensitivity Assay Based on ATP-Bioluminescence and Cell Cycle Perturbations Detected by Flow Cytometry. G. BOIKE, H. AvmwrE. C. Gom.m, AND R. RAMOS, University of Miami, Miami, Florida 33101. Historically, there has been tremendous interest in methods to predict tumor radiosensitivity and curability. Recent efforts have concentrated on various short-term in vitro sensitivity assays and flow cytometric measurements of proliferation kinetics and ploidy. The purpose of our study was to evaluate the correlation between radiation-induced cytotoxicity determined with the ATP-bioluminescence assay (Gynecol. Uncol. 31, IYl. 1988) and cell cycle perturbations detected with dualparameter flow cytometry (Gynecol. Oncol. 32,282. 1988). Two cervical squamous cell carcinoma lines (ME-180 and SiHa) and one ovarian adenocarcinoma cell line (CaOv-3) were studied. All lines demonstrated radiation dose-dependent survival curves. The radiation doses for 50% inhibition of control ATP values (IC50) were: 3.56 Gray (Gy), 6.61 Gy, and 3.38 Gy for ME-IHO, SiHa, and CaOv-3. respectively. The magnitude of accumulation in the G2 phase of the cell cycle, maximal 24-48 hr after irradiation, was dose dependent in all cell lines studied. In the squamous cell lines there was good correlation between the radiosensitivity (ICSO) and the magnitude of G2 accumulation 24 or 48 hr after irradiation. The concurrent use of these two in vitro modalities may prove clinically useful in prospectively assessing tumor radiosensitivity and curability. 01. Phase II Trial of lfosfamide and Mesna in Chemotherapy-Naive Patients with Recurrent or Advanced Squamous Carcinoma of the Cervix. G. SUI.I.ON. J. BINSSING, W. MCGUIRE, AND T. PATTON, the Gynecologic Oncology Group (GOG). Philadelphia, Pennsylvania 19 107. A phase II trial of ifosfamide (IFX) and mesna was conducted by the GOG in patients with recurrent or advanced squamous carcinoma of the cervix who had not received prior chemotherapy. A starting dose of 1.5 g/m’ IFX iv daily for 5 days and 300 mg/m’ mesna iv q 4 hr times three doses daily after IFX were given. In patients who had received prior radiotherapy, the starting dose of IFX was reduced to I.2 g/m’. Fifty-six patients were entered. Two patients each are ineligible and inevaluable and five are too early. Forty-seven are evaluable for toxicity and 46 for response. Age range was 20-84 years. GOG performance status was O-1 for all but nine patients. Forty-one patients had prior radiotherapy. Seven patients (14.‘)) developed GOG grade 3 or 4 granulocytopcnia and two developed grade 3 thrombocytopenia. There were one complete and six partial responses (15.2%) and 25 patients (54.4%) with stable disease for at least 3 months on therapy. Although ifosfamide has activity in this group of chemotherapy-naive patients with squamous carcinoma of the cervix, the dose schedule utilized in this study fails to confirm the high response rate reported by other investigators. 92. Laser Skinning Vulvectomy for Vulvar Intraepithelial Neoplasia. T. SEDLACEK, AND W. BRADFORD, Pennsylvania Hospital, Philadelphia. Pennsylvania 19107. A retrospective review of vulvar intraepithelial neoplasia (VIN) treated by excision skinning vulvectomy was conducted. Thirty-nine patients underwent primary therapy for VIN by laser skinning vulvectomy between l/83 and 12/8Y. All patients underwent colposcopy and
ONCOLOGISTS-ABSTRACTS
189
biopsy 3 months after surgery; 1 patient was lost to follow up. Median follow up was 2 years. Recurrence was noted in 5 patients (12.8%). Previous lower genital tract treatment for human papilloma virus (HPV) or intraepithelial neoplasia was noted in 27 patients (70%). Positive resection margins were noted in 7 patients (18%); 6 of whom were disease free on subsequent colposcopy. No patients had invasive cancer in the vulvectomy specimen. Twenty-nine patients had a history of genital warts or positive HPV typing. Eleven of these 29 patients were HPV positive on dot blot (8 16/18, 2 31,33.35, 1 6/11). Cigarette smoking was reported in 22 of 35 patients who responded. Patients who recurred did not differ from patients treated successfully in age of coitarche. cigarette use, other sexually transmitted diseases, number of sexual partners, or HPV type, Excision skinning vulvectomy is an effective treatment modality for VIN and allows for histologic review of the surgical specimen. Y3. CAI25-A Potential Prognostic Indicator in Patients with Cervical Carcinoma? G. L. GOLDBERG, A. SKL.AR. A. ASHER, P. A. LEVINE, K. A. O’HANLAN, AND C. D. RUNOWICZ, Albert Einstein College of Medicine, Bronx, New York 10461. Despite widespread screening. invasive cervical cancer (CxCa) remains a significant problem in the U.S. Irrespective of the clinical stage or the treatment modality, monitoring of the actual disease status is difficult and unreliable. CA125 has been shown to be useful in the follow-up of patients (pts) with ovarian and endometrial carcinomas. We performed a retrospective analysis on 104 patients with CxCa. Preand post-therapy CA125 levels were available in 64 pts. At initial presentation 19 pts (30%) had levels >35 U/ml, 12 pts (19%) had levels 16-35 U/ml, and 33 pts (51%) had levels ~16 U/ml. Eleven pts had pre- and post-treatment levels >35 U/ml. Ten of these II pts died of disease and 1 pt is alive with persistent or recurrent disease. Of the 20 pts with elevated levels at presentation that reverted to normal after therapy, IY are clinically free of disease at 14-46 months (median 27 months). Of the 33 pts with normal pre- and post-therapy CA125 levels, 31 pts are clinically without evidence of disease. Two pts had increasing CA125 levels at follow-up, and both had disease recurrence. One is dead of disease at 7 months and 1 is alive with disease at 8 months. There was no correlation between the CA125 level and the tumor type, grade. or stage of disease. Our data suggest that pts with initially elevated CA125 levels that revert to normal after therapy have a favorable prognosis. Persistent elevation of the CA125 levels during and after therapy in pts with CxCa was associated with a poor prognosis. 94. Phase II Trial of High Dose Cisplatin (C) with Sodium Thiosulfate (STS) Protection in Patients with Advanced Carcinoma of the Cervix (ACC) Previously Untreated with Chemotherapy. B. REICHMAN, M. MARKMAN. T. HAKES, W. JONES, S. RUBIN, W. HOSKINS, AND J. L. LEWIS. JR.. Memorial Sloan-Kettering Cancer Center, New York, New York 10021. C is one of the most active single agents in the treatment of ACC. A previously reported Phase I trial showed that the dose of C could be significantly increased with the simultaneous administration of STS and also suggested enhanced activity in ACC (Proc. Asco. 7,55, 1988). On this basis the current trial was instituted to explore the role of dose intensity in ACC. C was given iv at 200 mg/m’ as a 2H infusion with iv STS at 3.3 mg/m’ 1 hr prior to C, and 6.6 mg/m’ during C infusion. Standard antiemetics and hydration of at least 2 liters of saline were given. Treatment was repeated monthly. Patients who had