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Tamoxifen therapy in recurrent epithelial ovarian carcinoma
GYNECOLOGIC
ONCOLOGY
27, 208-213 (1987)
Tamoxifen Therapy in Recurrent Epithelial Ovarian Carcinoma’ SHELDON Departments
A. WEINER, M.D.,* DAVID S. ALBERTS, M.D., EARL A. SURWIT, M.D., JOHN DAVIS, M.D., AND DAVID GROSSO, PH.D. of Obstetrics
and Gynecology, of Arizona,
Pathology, and the Arizona Tucson, Arizona 85724
Cancer Center,
University
Received February 20, 1986 Thirty-seven patients with recurrent epithelial ovarian carcinoma were entered into a trial of tamoxifen therapy (10 mg BID) to determine the effect on long-term survival. Thirty-one patients were evaluable with follow-up ranging from 6 to 42 months since initiation of hormonal therapy. All patients were heavily pretreated with multiple chemotherapeutic regimens (median 3). There was 1 complete responder (3.2%), 2/31 (6.4%) had a partial response, 6/31 (19.3%) had stable disease, and 22/31 (71%) had progressive disease. Twenty-four patients are dead (23 from advanced carcinoma, 1 from cardiac causes); 5 patients are alive with disease; 2 patients are lost to follow-up. Median survival of nonresponders was 7 months versus 16months for responders (CR + PR + stable disease) (P = 0.001 life table analysis). Of the 9 responders, 7 had poorly differentiated tumors (grades 3 or 4), and 2 had moderately differentiated tumors (grade 2). Eleven patients had estrogen and progesterone receptor studies (ER, PR). No correlation between response rate and receptor status was evident. We conclude that although significant disease regression is unlikely to result from tamoxifen therapy, there may be a subset of patients who can benefit from the cytostatic properties of hormonal manipulation. Q 1987 Academic press, IIK.
INTRODUCTION The demonstration that antiestrogens can cause significant disease regression in metastatic breast cancer [l] has prompted researchers to search for other malignant neoplasms that may respond to hormonal manipulation. Numerous studies have confirmed that approximately 50% of ovarian carcinomas are estrogen receptor positive [2-51 and a few investigators have reported activity of progestins in the treatment of metastatic disease [3,6-S]. To evaluate whether antiestrogen therapy might possess similar activity in advanced, drug refactory ovarian carcinoma, we undertook a phase II trial of tamoxifen to evaluate response rate and effect on overall survival. This report examines our 5-year experience with this agent. ’ Supported in part by Grants CA-17094 and CA-23074 from the National Institutes of Health, Bethesda, MD 20205. Presented at the 13th Annual Western Association of Gynecologic Oncologists Meeting, San Diego, CA, June 1985. 2 To whom reprint requests should be addressed: Sinai Hospital of Detroit, Department of Obstetrics and Gynecology, 6767 W. Outer Dr. Detroit, MI 48235. 208 0090-8258187$1.50 Copyright All rights
0 1987 by Academic press, Inc. of reproduction in any form reserved.
TAMOXIFEN
IN
OVARIAN
CARCINOMA
209
MATERIALS AND METHODS Thirty-seven patients were enrolled in this prospective trial from 1979 to 1984. AU patients had biopsy proven epithelial ovarian carcinoma and had failed standard cytotoxic therapy. Each patient had measurable disease at the start of treatment. Tamoxifen was administered 40 mg/m* po qd x 7 followed by 10 mg po bid until documentation of disease progression. Patients were followed at monthly intervals with physical examination, routine laboratory tests, and radiographs as indicated. Patients were considered evaluable if they received a minimum of 4 weeks of therapy. Responses were defined as follows: (1) Complete response (CR): disappearance of all measurable disease for a minimum of 1 month. (2) Partial response (PR): a 50% decrease or greater of all measurable disease for a minimum of 1 month. (3) Stable disease (SD): a less than 50% decrease or a less than 25% increase in all measurable disease for a minimum of 2 months. (4) Progressive disease (PD): a greater than 25% increase in all measurable disease or the appearance of any new lesions. Receptor analyses. Receptor analyses were performed using the dextran-coated charcoal method described by others [9,10], using [3H]estradiol or [3H]R5020 for estrogen and progesterone receptors, respectively. Statistics. Survival curves were generated using the Kaplan-Meier life table analysis and P values calculated using the Log-Rank test.
RESULTS Of 37 patients who were entered into the trial, 31 are evaluable. Of the 6 nonevaluable patients, 2 were lost to follow-up prior to response assessment, 3 received tamoxifen for less than 4 weeks, and 1 had a coexistent second primary malignancy. There was 1 complete responder (3.2%), 2/31 (6.4%) had a partial response, 6/31 (19.3%) had stable disease, and 22/31 (71%) had progressive disease. Twenty-four of the 31 evaluable patients are dead, 23 from progressive disease, 1 from cardiac causes; 5 patients are alive with disease, 2 have been lost to follow-up. Median survival of nonresponders from the time of treatment was 7 months versus 16 months for responders (CR + PR + stable disease), P = 0.001 (Fig. 1). Median survival of nonresponders from the time of diagnosis was 30 months versus 49 months for responders (P < 0.008) (Fig. 2). Median duration of response was 14 months (range 3-23 months). A comparison of the two groups reveals similar prognostic variables. Sixtysix percent of responders had serous tumors versus 80% of nonresponders (Table 1). Seventy-seven percent of responders had grade 3 or 4 carcinomas versus 74% of nonresponders (Table 2). Responders tended to be slightly older, with a median age of 65 years versus 56.5 years for nonresponders. All patients were
210
ET AL.
WEINER
0.20Tu,l WI 9 4 A RESPONSE 22 20 . NOFcE.sPOw
O.lOo.oo-
, 12
0
, 24
, 36
, 46
, 80
, 72
I 04
, 96
tvlons FIG. 1.
Survival of ovarian patients treated with tamoxifen by time from treatment.
1.00 0.90 0.80 0.70 s'H
0.60
g P
0.50 Tom RI,
1;
0 a nREsmNsE 22 20 . NOREsPONsE
0.30 0.20 0.10 j40!
FIG. 2.
(\
Survival of ovarian patients treated with tamoxifen by time from
TABLE
1
RESFQNSEvs HISTOLOGY
Serous Mutinous Endometroid Undifferentiated Mixed Total
Responders
Nonresponders
6 0 2 0 1
16 1 1 2 0
9
20
TAMOXIFEN
IN
OVARIAN
211
CARCINOMA
TABLE 2 RESPONSEvs GRADE
Grade
Responders
1 2 3 4
0 2 5 2
1 4 I 7
9
19
Total
Nonresponders
heavily pretreated with multiple chemotherapeutic regimens (median 3). Fiftyfive and a half percent of responders were resistant to primary chemotherapy as were 68% of nonresponders (Table 3). The interval from diagnosis to treatment with tamoxifen was 32 months in responders versus 21t months in nonresponders. While most patients had multiple sites of recurrent disease, approximately three-fourths of the patients in both groups had measurable disease in the pelvis and/or abdomen (Table 4). Of potential prognostic importance is the fact that nonresponders were more likely to have ascites than responders, however, small patient numbers prevent any meaningful statistical analysis. Eleven patients had receptor studies done at some time during the course of their disease. Three patients had primary tumors available for analysis, eight patients had studies performed on metastatic lesions. Of these eight, six specimens were obtained prior to tamoxifen therapy, two were obtained subsequent to hormonal management. Three patients were ER positive PR positive. Five patients were ER negative PR negative, the remaining three had mixed findings (Table 5). Receptor status did not appear to be predictive of response rate. DISCUSSION Recent advances utilizing &-platinum containing combination chemotherapeutic regimens have yielded impressive response rates in primary, untreated epithelial ovarian carcinomas. However, long-term survival benefits have yet to be established [ll]. Stanhope has reported on the dismal response rates associated with second and third line chemotherapy, with third line agents yielding a 1.3% objective response rate [12]. While significant disease regression was also limited in this TABLE 3 RESPONSETO TAMOXIFEN vs RESPONSETO PRIMARY THERAPY
Primary therapy
Responders
NR PR CR (pathological) CR (clinical)
5 (55.5%) 2 (22.2) 1 (11.1) 1 (11.1)
15 (68.1%) 6 (27.2) I (4.5) 0
9
22
Total
Nonresponders
212
WEINER
ET AL.
TABLE 4 RESPONSE TO TAMOXIFENvs SITE OF RECURRENCE Nonresponders
Responders Ascites Retroperitoneal nodes Distant nodes Liver Pelvis Abdomen Pleural effusion Skin Vagina Lung
7122 (31.8%) 4/22 (18.1) 5122 (22.7) 3/22 (13.6) 11/22 (50) 7/22 (31.8) l/22 (4.5) l/22 (4.5) l/22 (4.5) 2122 (9)
l/9 (11.1%) O/9 (0) 219 (22.2) l/9 (11.1) 419 (44.4) 219 (22.2) O/9 (0) o/9 (0) 219 (22.2) l/9 (11.1)
phase II trial, approximately 30% of patients may have derived some benefit from disease stabilization. In a preliminary report of 13 patients, Schwartz reported similar findings; 1 patient had a partial response, and 4 patients had disease stabilization [13]. He, too, noted a survival advantage for the group of responders, but cautioned that the two groups may not be comparable. This same group of investigators has demonstrated the ability of tamoxifen to inhibit tumor colony formation of ovarian carcinomas in vitro [ 141. Shirey has recently reported on 23 patients similarly treated with tamoxifen for ovarian carcinoma [15]. No complete or partial responses were seen, but they did note an 82.6% disease stabilization rate. Other limited clinical trials utilizing progestins have confirmed that hormonal manipulation can result in disease regression or stabilization in a small subset of patients [3,6-g]. Whether the survival advantage seen in our series represents therapeutic gain, as opposed to an inherently less aggressive disease, remains to be determined. The groups appear to be comparable with regards to histology, grade, and sensitivity to cytotoxic therapy. The nonresponders did have a greater percentage of patients with ascites, a finding reported to be associated with a poorer prognosis [16]. However, responders tended to be older, and the interval from diagnosis to treatment was longer, factors which could have resulted in a decreased survival advantage, when in fact, the opposite was observed. Obviously, controlled trials will be needed to resolve these questions. TABLE 5 RESPONSE vs RECEPTOR STATUS
ER+ ERER+ ER-
PR+ PRPRPR+
Total
PR
Stable
Progress
Total
0 0 0 0
1 1 1 0
2 4 0 2
3 5 1 2
0
3
8
11
TAMOXIFEN
IN
OVARIAN
CARCINOMA
213
While the presence of estrogen receptors in ovarian carcinoma has been well documented [2-51, their ability to predict clinical response has not been well studied. Equally controversial is the quantitative value chosen to represent receptor positivity. The number of patients with receptors in our series is far too small to be able to draw any significant conclusions; however, no obvious correlation between response rate and receptor status was evident. In summary, patients with recurrent epithelial ovarian carcinoma are unlikely to have significant disease regression following tamoxifen therapy. There may be a subset of patients who will benefit from the cytostatic properties of hormonal manipulation. Controlled trials are needed to ascertain whether this survival benefit is indeed the result of tamoxifen therapy, and to better define which group of patients are likely to benefit from this treatment modality. REFERENCES 1. Taznon, H. Antiestrogens in the treatment of breast cancer, Cancer 39, 2959 (1977). 2. Kauppila, A., Vierikko, P., Kivinen, S., Stenback, F., and Vihko, R. Clinical significance of estrogen and progestin receptors in ovarian cancer, Obsret. Gynecol. 61, 320-326 (1983). 3. Bergqvist, A., Kullander, S., and Thorell, J. A study of estrogen and progesterone cytosol receptor concentration in benign and malignant ovarian tumors and a review of malignant ovarian tumors treated with medroxy-progesterone acetate, Acfa Obster. Gynecol. Stand. Suppl. 101, 75-81 (1981).
4. Janne, O., Kauppila, A., Syrjala, P., and Vihko, R. Comparison of cytosol estrogen and progestin receptor status in malignant and benign tumors and tumor-like lesions of human ovary, Int. J. Cancer 25, 175-179 (1980).
5. Schwartz, P. E., LiVolsi, V. A., Hildreth, N., MacLusky, N. J., Naftolin, F. N., and Eisenfeld, A. J. Estrogen receptors in ovarian epithelial carcinoma, Obstet. Gynecol. 59. 229-238 (1982). 6. Geisler, H. Megestrol acetate for the palliation of advanced ovarian carcinoma, Obstet. Gynecol. 61, 95-98 (1983).
7. Mangioni, C., Franceschi, S., LaVecchia, C., and D’Incalci, M. High-dose medroxyprogesterone acetate (MPA) in advanced epithelial ovarian cancer resistent to first- or second-line chemotherapy, Gynecol. Oncol. 12, 314-318 (1981). 8. Jolles, C. J., Freedman, R. S., and Jones, L. A. Estrogen and progestogen therapy in advanced ovarian cancer: preliminary report, Gynecol. Oncol. 16, 352-359 (1983). 9. Schrader, W. Y., Smith, K. G., and Coty, W. A. Hormone action and molecular endocrinology (B. W. O’Malley and W. T. Schrader, Eds.), Texas Health Sciences Center Printing Office, Houston. 10. Walters, M. R., and Clark, J. H. Cytosol progesterone receptors of the rat uterus: assay and receptor characteristics, J. Sreroid Rio&em. 8, 1137-1144 (1977). 11. Brenner, D. E., and Greco, F. A. Multiagent chemotherapy in advanced ovarian carcinoma, in Ovarian cancer, Martinus Nijhoff Publishers, Boston, pp. 147-177 (1985). 12. Stanhope, R. C., Smith, J. P., and Rutledge, F. Second trial drugs in ovarian cancer, Gynecol. Oncol. 5, 52 (1977).
13. Schwartz, P. E., Keating, G., MacLusky, N., Naftolin, F., and Eisenfeld, A. Tamoxifen therapy for advanced ovarian cancer, Obstet. Gynecol. 59, 583-588 (1982). 14. Laze, J. S., Schwartz, P. E., MacLusky, N. J., Labaree, D. C., and Eisenfeld, A. J. Antiproliferative actions of tamoxifen to human ovarian carcinomas in vitro, Cancer Res. 44, 2266-2271 (1984). 15. Shirey, D. R., Kavanagh, J. J., Gershenson, D. M., Freedman, D. S., Copeland, L. J., and Jones, L. A. Tamoxifen therapy of epithelial ovarian cancer, Obstet. Gynecol. 66, 575-578 (1985). 16. Berek, J. S., Hacker, N. F., Lagasse, L. D., Nieberg, R. K., and Elashoff, R. M. Survival of patients following secondary cytoreductive surgery in ovarian cancer, Obsfet. Gynecol. 61, 189 (1983).
ONCOLOGY
27, 208-213 (1987)
Tamoxifen Therapy in Recurrent Epithelial Ovarian Carcinoma’ SHELDON Departments
A. WEINER, M.D.,* DAVID S. ALBERTS, M.D., EARL A. SURWIT, M.D., JOHN DAVIS, M.D., AND DAVID GROSSO, PH.D. of Obstetrics
and Gynecology, of Arizona,
Pathology, and the Arizona Tucson, Arizona 85724
Cancer Center,
University
Received February 20, 1986 Thirty-seven patients with recurrent epithelial ovarian carcinoma were entered into a trial of tamoxifen therapy (10 mg BID) to determine the effect on long-term survival. Thirty-one patients were evaluable with follow-up ranging from 6 to 42 months since initiation of hormonal therapy. All patients were heavily pretreated with multiple chemotherapeutic regimens (median 3). There was 1 complete responder (3.2%), 2/31 (6.4%) had a partial response, 6/31 (19.3%) had stable disease, and 22/31 (71%) had progressive disease. Twenty-four patients are dead (23 from advanced carcinoma, 1 from cardiac causes); 5 patients are alive with disease; 2 patients are lost to follow-up. Median survival of nonresponders was 7 months versus 16months for responders (CR + PR + stable disease) (P = 0.001 life table analysis). Of the 9 responders, 7 had poorly differentiated tumors (grades 3 or 4), and 2 had moderately differentiated tumors (grade 2). Eleven patients had estrogen and progesterone receptor studies (ER, PR). No correlation between response rate and receptor status was evident. We conclude that although significant disease regression is unlikely to result from tamoxifen therapy, there may be a subset of patients who can benefit from the cytostatic properties of hormonal manipulation. Q 1987 Academic press, IIK.
INTRODUCTION The demonstration that antiestrogens can cause significant disease regression in metastatic breast cancer [l] has prompted researchers to search for other malignant neoplasms that may respond to hormonal manipulation. Numerous studies have confirmed that approximately 50% of ovarian carcinomas are estrogen receptor positive [2-51 and a few investigators have reported activity of progestins in the treatment of metastatic disease [3,6-S]. To evaluate whether antiestrogen therapy might possess similar activity in advanced, drug refactory ovarian carcinoma, we undertook a phase II trial of tamoxifen to evaluate response rate and effect on overall survival. This report examines our 5-year experience with this agent. ’ Supported in part by Grants CA-17094 and CA-23074 from the National Institutes of Health, Bethesda, MD 20205. Presented at the 13th Annual Western Association of Gynecologic Oncologists Meeting, San Diego, CA, June 1985. 2 To whom reprint requests should be addressed: Sinai Hospital of Detroit, Department of Obstetrics and Gynecology, 6767 W. Outer Dr. Detroit, MI 48235. 208 0090-8258187$1.50 Copyright All rights
0 1987 by Academic press, Inc. of reproduction in any form reserved.
TAMOXIFEN
IN
OVARIAN
CARCINOMA
209
MATERIALS AND METHODS Thirty-seven patients were enrolled in this prospective trial from 1979 to 1984. AU patients had biopsy proven epithelial ovarian carcinoma and had failed standard cytotoxic therapy. Each patient had measurable disease at the start of treatment. Tamoxifen was administered 40 mg/m* po qd x 7 followed by 10 mg po bid until documentation of disease progression. Patients were followed at monthly intervals with physical examination, routine laboratory tests, and radiographs as indicated. Patients were considered evaluable if they received a minimum of 4 weeks of therapy. Responses were defined as follows: (1) Complete response (CR): disappearance of all measurable disease for a minimum of 1 month. (2) Partial response (PR): a 50% decrease or greater of all measurable disease for a minimum of 1 month. (3) Stable disease (SD): a less than 50% decrease or a less than 25% increase in all measurable disease for a minimum of 2 months. (4) Progressive disease (PD): a greater than 25% increase in all measurable disease or the appearance of any new lesions. Receptor analyses. Receptor analyses were performed using the dextran-coated charcoal method described by others [9,10], using [3H]estradiol or [3H]R5020 for estrogen and progesterone receptors, respectively. Statistics. Survival curves were generated using the Kaplan-Meier life table analysis and P values calculated using the Log-Rank test.
RESULTS Of 37 patients who were entered into the trial, 31 are evaluable. Of the 6 nonevaluable patients, 2 were lost to follow-up prior to response assessment, 3 received tamoxifen for less than 4 weeks, and 1 had a coexistent second primary malignancy. There was 1 complete responder (3.2%), 2/31 (6.4%) had a partial response, 6/31 (19.3%) had stable disease, and 22/31 (71%) had progressive disease. Twenty-four of the 31 evaluable patients are dead, 23 from progressive disease, 1 from cardiac causes; 5 patients are alive with disease, 2 have been lost to follow-up. Median survival of nonresponders from the time of treatment was 7 months versus 16 months for responders (CR + PR + stable disease), P = 0.001 (Fig. 1). Median survival of nonresponders from the time of diagnosis was 30 months versus 49 months for responders (P < 0.008) (Fig. 2). Median duration of response was 14 months (range 3-23 months). A comparison of the two groups reveals similar prognostic variables. Sixtysix percent of responders had serous tumors versus 80% of nonresponders (Table 1). Seventy-seven percent of responders had grade 3 or 4 carcinomas versus 74% of nonresponders (Table 2). Responders tended to be slightly older, with a median age of 65 years versus 56.5 years for nonresponders. All patients were
210
ET AL.
WEINER
0.20Tu,l WI 9 4 A RESPONSE 22 20 . NOFcE.sPOw
O.lOo.oo-
, 12
0
, 24
, 36
, 46
, 80
, 72
I 04
, 96
tvlons FIG. 1.
Survival of ovarian patients treated with tamoxifen by time from treatment.
1.00 0.90 0.80 0.70 s'H
0.60
g P
0.50 Tom RI,
1;
0 a nREsmNsE 22 20 . NOREsPONsE
0.30 0.20 0.10 j40!
FIG. 2.
(\
Survival of ovarian patients treated with tamoxifen by time from
TABLE
1
RESFQNSEvs HISTOLOGY
Serous Mutinous Endometroid Undifferentiated Mixed Total
Responders
Nonresponders
6 0 2 0 1
16 1 1 2 0
9
20
TAMOXIFEN
IN
OVARIAN
211
CARCINOMA
TABLE 2 RESPONSEvs GRADE
Grade
Responders
1 2 3 4
0 2 5 2
1 4 I 7
9
19
Total
Nonresponders
heavily pretreated with multiple chemotherapeutic regimens (median 3). Fiftyfive and a half percent of responders were resistant to primary chemotherapy as were 68% of nonresponders (Table 3). The interval from diagnosis to treatment with tamoxifen was 32 months in responders versus 21t months in nonresponders. While most patients had multiple sites of recurrent disease, approximately three-fourths of the patients in both groups had measurable disease in the pelvis and/or abdomen (Table 4). Of potential prognostic importance is the fact that nonresponders were more likely to have ascites than responders, however, small patient numbers prevent any meaningful statistical analysis. Eleven patients had receptor studies done at some time during the course of their disease. Three patients had primary tumors available for analysis, eight patients had studies performed on metastatic lesions. Of these eight, six specimens were obtained prior to tamoxifen therapy, two were obtained subsequent to hormonal management. Three patients were ER positive PR positive. Five patients were ER negative PR negative, the remaining three had mixed findings (Table 5). Receptor status did not appear to be predictive of response rate. DISCUSSION Recent advances utilizing &-platinum containing combination chemotherapeutic regimens have yielded impressive response rates in primary, untreated epithelial ovarian carcinomas. However, long-term survival benefits have yet to be established [ll]. Stanhope has reported on the dismal response rates associated with second and third line chemotherapy, with third line agents yielding a 1.3% objective response rate [12]. While significant disease regression was also limited in this TABLE 3 RESPONSETO TAMOXIFEN vs RESPONSETO PRIMARY THERAPY
Primary therapy
Responders
NR PR CR (pathological) CR (clinical)
5 (55.5%) 2 (22.2) 1 (11.1) 1 (11.1)
15 (68.1%) 6 (27.2) I (4.5) 0
9
22
Total
Nonresponders
212
WEINER
ET AL.
TABLE 4 RESPONSE TO TAMOXIFENvs SITE OF RECURRENCE Nonresponders
Responders Ascites Retroperitoneal nodes Distant nodes Liver Pelvis Abdomen Pleural effusion Skin Vagina Lung
7122 (31.8%) 4/22 (18.1) 5122 (22.7) 3/22 (13.6) 11/22 (50) 7/22 (31.8) l/22 (4.5) l/22 (4.5) l/22 (4.5) 2122 (9)
l/9 (11.1%) O/9 (0) 219 (22.2) l/9 (11.1) 419 (44.4) 219 (22.2) O/9 (0) o/9 (0) 219 (22.2) l/9 (11.1)
phase II trial, approximately 30% of patients may have derived some benefit from disease stabilization. In a preliminary report of 13 patients, Schwartz reported similar findings; 1 patient had a partial response, and 4 patients had disease stabilization [13]. He, too, noted a survival advantage for the group of responders, but cautioned that the two groups may not be comparable. This same group of investigators has demonstrated the ability of tamoxifen to inhibit tumor colony formation of ovarian carcinomas in vitro [ 141. Shirey has recently reported on 23 patients similarly treated with tamoxifen for ovarian carcinoma [15]. No complete or partial responses were seen, but they did note an 82.6% disease stabilization rate. Other limited clinical trials utilizing progestins have confirmed that hormonal manipulation can result in disease regression or stabilization in a small subset of patients [3,6-g]. Whether the survival advantage seen in our series represents therapeutic gain, as opposed to an inherently less aggressive disease, remains to be determined. The groups appear to be comparable with regards to histology, grade, and sensitivity to cytotoxic therapy. The nonresponders did have a greater percentage of patients with ascites, a finding reported to be associated with a poorer prognosis [16]. However, responders tended to be older, and the interval from diagnosis to treatment was longer, factors which could have resulted in a decreased survival advantage, when in fact, the opposite was observed. Obviously, controlled trials will be needed to resolve these questions. TABLE 5 RESPONSE vs RECEPTOR STATUS
ER+ ERER+ ER-
PR+ PRPRPR+
Total
PR
Stable
Progress
Total
0 0 0 0
1 1 1 0
2 4 0 2
3 5 1 2
0
3
8
11
TAMOXIFEN
IN
OVARIAN
CARCINOMA
213
While the presence of estrogen receptors in ovarian carcinoma has been well documented [2-51, their ability to predict clinical response has not been well studied. Equally controversial is the quantitative value chosen to represent receptor positivity. The number of patients with receptors in our series is far too small to be able to draw any significant conclusions; however, no obvious correlation between response rate and receptor status was evident. In summary, patients with recurrent epithelial ovarian carcinoma are unlikely to have significant disease regression following tamoxifen therapy. There may be a subset of patients who will benefit from the cytostatic properties of hormonal manipulation. Controlled trials are needed to ascertain whether this survival benefit is indeed the result of tamoxifen therapy, and to better define which group of patients are likely to benefit from this treatment modality. REFERENCES 1. Taznon, H. Antiestrogens in the treatment of breast cancer, Cancer 39, 2959 (1977). 2. Kauppila, A., Vierikko, P., Kivinen, S., Stenback, F., and Vihko, R. Clinical significance of estrogen and progestin receptors in ovarian cancer, Obsret. Gynecol. 61, 320-326 (1983). 3. Bergqvist, A., Kullander, S., and Thorell, J. A study of estrogen and progesterone cytosol receptor concentration in benign and malignant ovarian tumors and a review of malignant ovarian tumors treated with medroxy-progesterone acetate, Acfa Obster. Gynecol. Stand. Suppl. 101, 75-81 (1981).
4. Janne, O., Kauppila, A., Syrjala, P., and Vihko, R. Comparison of cytosol estrogen and progestin receptor status in malignant and benign tumors and tumor-like lesions of human ovary, Int. J. Cancer 25, 175-179 (1980).
5. Schwartz, P. E., LiVolsi, V. A., Hildreth, N., MacLusky, N. J., Naftolin, F. N., and Eisenfeld, A. J. Estrogen receptors in ovarian epithelial carcinoma, Obstet. Gynecol. 59. 229-238 (1982). 6. Geisler, H. Megestrol acetate for the palliation of advanced ovarian carcinoma, Obstet. Gynecol. 61, 95-98 (1983).
7. Mangioni, C., Franceschi, S., LaVecchia, C., and D’Incalci, M. High-dose medroxyprogesterone acetate (MPA) in advanced epithelial ovarian cancer resistent to first- or second-line chemotherapy, Gynecol. Oncol. 12, 314-318 (1981). 8. Jolles, C. J., Freedman, R. S., and Jones, L. A. Estrogen and progestogen therapy in advanced ovarian cancer: preliminary report, Gynecol. Oncol. 16, 352-359 (1983). 9. Schrader, W. Y., Smith, K. G., and Coty, W. A. Hormone action and molecular endocrinology (B. W. O’Malley and W. T. Schrader, Eds.), Texas Health Sciences Center Printing Office, Houston. 10. Walters, M. R., and Clark, J. H. Cytosol progesterone receptors of the rat uterus: assay and receptor characteristics, J. Sreroid Rio&em. 8, 1137-1144 (1977). 11. Brenner, D. E., and Greco, F. A. Multiagent chemotherapy in advanced ovarian carcinoma, in Ovarian cancer, Martinus Nijhoff Publishers, Boston, pp. 147-177 (1985). 12. Stanhope, R. C., Smith, J. P., and Rutledge, F. Second trial drugs in ovarian cancer, Gynecol. Oncol. 5, 52 (1977).
13. Schwartz, P. E., Keating, G., MacLusky, N., Naftolin, F., and Eisenfeld, A. Tamoxifen therapy for advanced ovarian cancer, Obstet. Gynecol. 59, 583-588 (1982). 14. Laze, J. S., Schwartz, P. E., MacLusky, N. J., Labaree, D. C., and Eisenfeld, A. J. Antiproliferative actions of tamoxifen to human ovarian carcinomas in vitro, Cancer Res. 44, 2266-2271 (1984). 15. Shirey, D. R., Kavanagh, J. J., Gershenson, D. M., Freedman, D. S., Copeland, L. J., and Jones, L. A. Tamoxifen therapy of epithelial ovarian cancer, Obstet. Gynecol. 66, 575-578 (1985). 16. Berek, J. S., Hacker, N. F., Lagasse, L. D., Nieberg, R. K., and Elashoff, R. M. Survival of patients following secondary cytoreductive surgery in ovarian cancer, Obsfet. Gynecol. 61, 189 (1983).