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Cyclophosphamide (C), adriamycin (A) and cisplatin (P) as second line chemotherapy (CH) of epithelial ovarian cancer (EOC): Mature results in 118 patients (Pts)
110
SOCIETY OF GYNECOLOGIC
One hundred twenty-three patients (pts) with primary ovarian carcinoma were tested by immunoradiometric assay (IRMA) for the tumor marker CA 125. CA 125 serum values correlated well with tumor burden: 28% positive cases for tumor diameter <2 cm, 50% for 2-5 cm, 94% for 5-10 cm, and 100% for >lO cm. Regarding follow-up, CA 125 serum level increase preceded relapse even by as much as 911 months in two cases. Ten surgically treated pts with clinical evidence of residual carcinoma (second look positive) also showed IRMA positive, while only 4 out of 8 NED (second look positive) pts. had CA 125 serum level >35 U/ml. IRMA, preoperatory immunoscintigraphy with “‘I- or “‘In labeled OC 125 (IS), radiometry on tumor fragments, and immunocytochemistry (ICC) (ABC immunoperoxidase) were performed in 19 pts presenting pelvic mass and in 4 second look ovarian carcinoma pts. Tumor-associated antigen TAG-72 was studied through IS and ICC in an additional series of 10 pts with pelvic mass, 5 pts with uterine neoplasia, and 4 second look ovarian carcinoma pts. For both markers, IS and ICC findings appeared well correlated; they also showed positive in three myomas and in two ovarian adenofibromas of the CA 125 series, but in these cases ICC displayed a diffuse, not membranerelated, cytoplasmic reactivity and IRMA was in the <60 U/ml range. No correlation was found between ICC and the focal or diffuse mode of IS. All CA 125 ICC-positive cases showed a significant radiotracer uptake. Both CA 125 and TAG-72 presented as non specific mtillerian antigens; TAG-72 appeared more malignancy related (the only exception was a TAG-72 IS-ICC-positive uterine myoma). This research is in progress on a larger prospective series.
ONCOLOGISTS-ABSTRACTS 68. Cisplatin (P), Vinblastine (V), and Bleomycin (B) Combination Chemotherapy in Recurrent or Advanced Granulosa Cell Tumor of the Ovary (GCTO): An Eortc Gynecology Cancer Cooperafive Group Study. S. PECORELLI,P. WAGENER, C. BONAZZI, W. TEN BOKKEL HUININK, N. COLOMBO, G. FAVALLI, A. KOBIERSKA, E. PLOCH, C. N. VEENHOF,R. WILLEMZE, N. ROTMENSZ,AND J. B.
VERMORKEN, Clinica Ostetrica Ginecologica Universita di Brescia, 25125 Bresica, Italy.
A phase II study was performed to assess the activity of PVB in patients (pts) with GCTO, either recurrent or advanced, when conventional treatments like surgery (S) and radiotherapy (RT) had fully been used or were inappropriate. From December of 1984, 32 pts entered the study: 13 pts were fully evaluable and 2 were for toxicity only. The median age was 59 (range: 7-70) and the performance status was 0 (WHO: O-2). Prior treatment consisted of S in 11 pts and S + RT in 4; 1 pt had received previous chemotherapy. Nine pts had recurrent disease, 5 were stage III, and 1 was stage IV. PVB consisted of: P 20 mg/m’ iv Day l-5; V 0, 15 mg/kg iv (in previously irradiated pts: 0.10 mg/kg) Day 1-2; B 30 mg (24 hr infusion) Day 2 and 15 mg iv or im Day 15; q 28 days, for four cycles. Twelve of thirteen pts responded to PVB (92%) for a duration of 2 to 29+ months in case of complete response (CR =7) and 5 + to 47 + months for partial responders (PR = 5). One stage III pt (juvenile type) showed no response and rapidly died. Hematological (H) and non H toxicity were severe, with median WBC nadir of 14OO/~l (800-2200) occurring on Day 14 of a median cycle 3 and median platelet nadir of 67,000/~1 (26,000108,000) on Day 12 of a median cycle 3. Non H toxicity included: 67. Cyclophosphamide (C), Adriamycin (A) and Cispfatin (P) as Second nausea and vomiting in 14/15 (WHO grade 3:8); alopecia in 11 (grade Line Chemotherapy (CH) of Epithelial Ovarian Cancer (EOC): 3:6); diarrhea in 6 (grade 3:l); fever in 6; infection in 5 (grade 4:l); Mature Results in 118 Patients (Pts). N. COLOMBO, A. EPIS, S. and skin toxicity in I (grade 3). One patient experienced peripheral CHIARI,F. LANDONI,S. LOMONICO,C. MANGIONI,S. GERARDO,AND neurotoxicity grade 3 with severe hypokalemia and 1 pt had a paralitic H. MONZA, University of Milan, Milan, Italy. ileus. PVB is an active regimen for GCTO. Though observation time From May 1982 to May 1987 we treated with CAP 118 patients (pts) is still too short, it seems that PVB may produce long remissions with with stage (st) III-IV EOC persistent after P-based first-line CH. Previous 6 pts out of 13 still disease free at a follow-up of 8 to 47 months. treatment included: monoCH with P or carboplatin in 51%; C and P in 12%; and A, C, and P in 37%. Mean P dose of first-line CH was 69. The Association of Human Papillomavirus with Vulvar Neoplasms. 340 mg/m’. Residual tumor diameters at second look before CAP were J. WALKER, S. WILCZYNSKI, M. PEAKE, R. MANNEL, M. BERMAN, microscopic in 31%, < 1 cm in 26%, l-2 cm in 18%, >2 cm in 7%, AND P. DISAIA, Departments of Obstetrics, Gynecology, and Paand not assessed in 18%. All but 15 pts had a partial response (PR) thology, University of California, Irvine, Orange, California 92668. to first line CH. CAP regimen (C=600 mg/m’, A=50 mg/m2, P = 50 Eighteen vulvar neoplasms were studied for the presence of human mg/m’ was given for a median of five cycles (range, 3-7). The median papillomavirus (HPV) by Southern blot DNA hybridization technique. follow up time is 35 months. Complete response (CR) and PR are Type specific DNA probes were individually tested with DNA from reported according to response to first-line CH: each neoplasm and only HPV 16 was detected, none contained HPV Response to PAC 6, 11, 18, or 31 DNA. Four of the five (80%) vulvar intraepithelial neoplasias (VIN) contained HPV 16 DNA and it was noted to be in Pathological episomal form. Only 3 of the 13 (23%) squamous cell carcinomas of the vulva contained HPV 16 DNA. The presence of viral DNA within Clinical PR CR the majority of preinvasive vulvar lesions and very few of the invasive Response to first line (N) (M 09 squamous cell carcinomas suggests that the viral DNA may be important only during transformation, and then does not persist in the tumor 10 0 13 PR micro (34) cells or that there is a separate etiology for the majority of the invasive 13 4 12 PR macro (51) squamous cell carcinomas of the vulva. 4 5 4 Clinical PR (18) 2 3 0 No response (l5) ’ No evidence of disease. The median progression-free survival (PFS) and survival (S) from second look were significantly longer (P < 0.001) for pts with microscopic disease (PFS = 26 months, S = 31 months) compared to pts with macroscopic tumor (PFS = 12 months; S = 14 months). No difference in PFS, nor in S, was observed according to type and duration of firstline CH. Grade 3 and 4 myelotoxicities occurred in 20% of pts. Alopecia and nausea-vomiting were universal. The impact of first- and secondline CH on long-term survival is discussed.
70. Demonstration of Human Papillomavirus (HPV) in Primary, Metastatic, and Recurrent Cervical Carcinoma Using in Situ Hybridization. R. HOLLOWAY,G. LEWANDOWSKI, M. FARRELL,R. POTKUL,
A. JENSON,W. LANCASTER, ANDG. DELGADO,Georgetown University, Washington, D.C. 20007. HPV has been demonstrated in primary and metastatic cervical cancer using Southern blot hybridization; this technique does not permit precise localization of viral DNA to specific tissue or cell types. To better define the localization of HPV in metastatic and recurrent cervical carcinoma specimens, in situ hybridization (IHS) was used to type
SOCIETY OF GYNECOLOGIC
One hundred twenty-three patients (pts) with primary ovarian carcinoma were tested by immunoradiometric assay (IRMA) for the tumor marker CA 125. CA 125 serum values correlated well with tumor burden: 28% positive cases for tumor diameter <2 cm, 50% for 2-5 cm, 94% for 5-10 cm, and 100% for >lO cm. Regarding follow-up, CA 125 serum level increase preceded relapse even by as much as 911 months in two cases. Ten surgically treated pts with clinical evidence of residual carcinoma (second look positive) also showed IRMA positive, while only 4 out of 8 NED (second look positive) pts. had CA 125 serum level >35 U/ml. IRMA, preoperatory immunoscintigraphy with “‘I- or “‘In labeled OC 125 (IS), radiometry on tumor fragments, and immunocytochemistry (ICC) (ABC immunoperoxidase) were performed in 19 pts presenting pelvic mass and in 4 second look ovarian carcinoma pts. Tumor-associated antigen TAG-72 was studied through IS and ICC in an additional series of 10 pts with pelvic mass, 5 pts with uterine neoplasia, and 4 second look ovarian carcinoma pts. For both markers, IS and ICC findings appeared well correlated; they also showed positive in three myomas and in two ovarian adenofibromas of the CA 125 series, but in these cases ICC displayed a diffuse, not membranerelated, cytoplasmic reactivity and IRMA was in the <60 U/ml range. No correlation was found between ICC and the focal or diffuse mode of IS. All CA 125 ICC-positive cases showed a significant radiotracer uptake. Both CA 125 and TAG-72 presented as non specific mtillerian antigens; TAG-72 appeared more malignancy related (the only exception was a TAG-72 IS-ICC-positive uterine myoma). This research is in progress on a larger prospective series.
ONCOLOGISTS-ABSTRACTS 68. Cisplatin (P), Vinblastine (V), and Bleomycin (B) Combination Chemotherapy in Recurrent or Advanced Granulosa Cell Tumor of the Ovary (GCTO): An Eortc Gynecology Cancer Cooperafive Group Study. S. PECORELLI,P. WAGENER, C. BONAZZI, W. TEN BOKKEL HUININK, N. COLOMBO, G. FAVALLI, A. KOBIERSKA, E. PLOCH, C. N. VEENHOF,R. WILLEMZE, N. ROTMENSZ,AND J. B.
VERMORKEN, Clinica Ostetrica Ginecologica Universita di Brescia, 25125 Bresica, Italy.
A phase II study was performed to assess the activity of PVB in patients (pts) with GCTO, either recurrent or advanced, when conventional treatments like surgery (S) and radiotherapy (RT) had fully been used or were inappropriate. From December of 1984, 32 pts entered the study: 13 pts were fully evaluable and 2 were for toxicity only. The median age was 59 (range: 7-70) and the performance status was 0 (WHO: O-2). Prior treatment consisted of S in 11 pts and S + RT in 4; 1 pt had received previous chemotherapy. Nine pts had recurrent disease, 5 were stage III, and 1 was stage IV. PVB consisted of: P 20 mg/m’ iv Day l-5; V 0, 15 mg/kg iv (in previously irradiated pts: 0.10 mg/kg) Day 1-2; B 30 mg (24 hr infusion) Day 2 and 15 mg iv or im Day 15; q 28 days, for four cycles. Twelve of thirteen pts responded to PVB (92%) for a duration of 2 to 29+ months in case of complete response (CR =7) and 5 + to 47 + months for partial responders (PR = 5). One stage III pt (juvenile type) showed no response and rapidly died. Hematological (H) and non H toxicity were severe, with median WBC nadir of 14OO/~l (800-2200) occurring on Day 14 of a median cycle 3 and median platelet nadir of 67,000/~1 (26,000108,000) on Day 12 of a median cycle 3. Non H toxicity included: 67. Cyclophosphamide (C), Adriamycin (A) and Cispfatin (P) as Second nausea and vomiting in 14/15 (WHO grade 3:8); alopecia in 11 (grade Line Chemotherapy (CH) of Epithelial Ovarian Cancer (EOC): 3:6); diarrhea in 6 (grade 3:l); fever in 6; infection in 5 (grade 4:l); Mature Results in 118 Patients (Pts). N. COLOMBO, A. EPIS, S. and skin toxicity in I (grade 3). One patient experienced peripheral CHIARI,F. LANDONI,S. LOMONICO,C. MANGIONI,S. GERARDO,AND neurotoxicity grade 3 with severe hypokalemia and 1 pt had a paralitic H. MONZA, University of Milan, Milan, Italy. ileus. PVB is an active regimen for GCTO. Though observation time From May 1982 to May 1987 we treated with CAP 118 patients (pts) is still too short, it seems that PVB may produce long remissions with with stage (st) III-IV EOC persistent after P-based first-line CH. Previous 6 pts out of 13 still disease free at a follow-up of 8 to 47 months. treatment included: monoCH with P or carboplatin in 51%; C and P in 12%; and A, C, and P in 37%. Mean P dose of first-line CH was 69. The Association of Human Papillomavirus with Vulvar Neoplasms. 340 mg/m’. Residual tumor diameters at second look before CAP were J. WALKER, S. WILCZYNSKI, M. PEAKE, R. MANNEL, M. BERMAN, microscopic in 31%, < 1 cm in 26%, l-2 cm in 18%, >2 cm in 7%, AND P. DISAIA, Departments of Obstetrics, Gynecology, and Paand not assessed in 18%. All but 15 pts had a partial response (PR) thology, University of California, Irvine, Orange, California 92668. to first line CH. CAP regimen (C=600 mg/m’, A=50 mg/m2, P = 50 Eighteen vulvar neoplasms were studied for the presence of human mg/m’ was given for a median of five cycles (range, 3-7). The median papillomavirus (HPV) by Southern blot DNA hybridization technique. follow up time is 35 months. Complete response (CR) and PR are Type specific DNA probes were individually tested with DNA from reported according to response to first-line CH: each neoplasm and only HPV 16 was detected, none contained HPV Response to PAC 6, 11, 18, or 31 DNA. Four of the five (80%) vulvar intraepithelial neoplasias (VIN) contained HPV 16 DNA and it was noted to be in Pathological episomal form. Only 3 of the 13 (23%) squamous cell carcinomas of the vulva contained HPV 16 DNA. The presence of viral DNA within Clinical PR CR the majority of preinvasive vulvar lesions and very few of the invasive Response to first line (N) (M 09 squamous cell carcinomas suggests that the viral DNA may be important only during transformation, and then does not persist in the tumor 10 0 13 PR micro (34) cells or that there is a separate etiology for the majority of the invasive 13 4 12 PR macro (51) squamous cell carcinomas of the vulva. 4 5 4 Clinical PR (18) 2 3 0 No response (l5) ’ No evidence of disease. The median progression-free survival (PFS) and survival (S) from second look were significantly longer (P < 0.001) for pts with microscopic disease (PFS = 26 months, S = 31 months) compared to pts with macroscopic tumor (PFS = 12 months; S = 14 months). No difference in PFS, nor in S, was observed according to type and duration of firstline CH. Grade 3 and 4 myelotoxicities occurred in 20% of pts. Alopecia and nausea-vomiting were universal. The impact of first- and secondline CH on long-term survival is discussed.
70. Demonstration of Human Papillomavirus (HPV) in Primary, Metastatic, and Recurrent Cervical Carcinoma Using in Situ Hybridization. R. HOLLOWAY,G. LEWANDOWSKI, M. FARRELL,R. POTKUL,
A. JENSON,W. LANCASTER, ANDG. DELGADO,Georgetown University, Washington, D.C. 20007. HPV has been demonstrated in primary and metastatic cervical cancer using Southern blot hybridization; this technique does not permit precise localization of viral DNA to specific tissue or cell types. To better define the localization of HPV in metastatic and recurrent cervical carcinoma specimens, in situ hybridization (IHS) was used to type