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Successful treatment of persistent partial mole with oral methotrexate therapy
GYNECOLOGIC ONCOLOGY 46,
233-234 (1992)
CASE REPORT Successful Treatment of Persistent Partial Mole with Oral Methotrexate Therapy BRUCE PATSNER, New Jersey Gynecologic
Oncology,
P.A., Riverview
M.D.
Medical Center, Red Bank, New Jersey 07701
Received August 23, 1991
Partial molar pregnancy is a relatively indolent form of hydatidiform mole commonly characterized by the presence of a fetus, mild hydropic villous swelling, focal trophoblastic hyperplasia, and a triploid genetic component [l]. Patients with partial mole often present as missed or incomplete abortion. The diagnosis may be suggested preevacuation by the ultrasonographic findings of both cystic changes in the decidua or placenta and a ratio of transverse to anteroposterior diameter of the gestational sac of greater than 1.5 [2]. The risk of developing gestational trophoblastic disease (GTD) following evacuation of partial molar pregnancy is low and reported to be about 4% (range, O-11%) [3]. Virtually all cases of persistent partial mole after uterine evacuation have been confined to the uterus, although one case of metastatic disease has been reported [4]. Treatment of persistent partial molar pregnancy has been successful in all casesand has consisted of traditional intravenous methotrexate with leucovorin rescue [5]. Intramuscular bleomycin has also been reported [6] to be effective, as has intravenous actinomycin D [7]. Oral methotrexate therapy has not been previously reported for treatment of persistent partial molar pregnancy. The present report describes two cases of successful use of oral methotrexate therapy to treat persistent trophoblast following evacuation of a partial molar pregnancy.
intrauterine gestation by abdominal ultrasound obtained because of vaginal spotting. A singleton pregnancy without fetal heartbeat was noted, as was a large sonolucent area within the placenta. Serum P-HCG was 213,000 mIU/ml. Repeat examination 2 weeks later revealed an S-week-size uterus, and repeat scan confirmed fetal demise. Dilatation and curettage were performed and curettings read as partial molar pregnancy, triploid on karyotype. Uterine involution postevacuation was complete, but serum /3-HCG rose from 6000 to 8000 mIU/ml 6 to 8 weeks postevacuation. Chest X ray was normal. Repeat uterine sonogram revealed a complex density in the fundus, with an area of sonolucency. The diagnosis of persistent partial molar pregnancy was made and the patient referred for evaluation. Prior to initiating therapy, pelvic examination revealed a soft, 4-week size uterus and serum /3-HCG was 9600 mIU/ml. All serum blood chemistries and complete blood count were normal. Oral contraceptive therapy was initiated and oral methotrexate, 25 mg/day for 5 days, with a planned 9-day window, was started. Serum /3-HCG levels after each of three courses of oral methotrexate therapy were 2000, 390, and 5 mIU/ml. Pelvic examination was normal, as were blood counts and chemistries at all times. Two days of vaginal spotting occurred at the start of each course of oral methotrexate but no stomatitis, nausea, or vomiting occurred. A final fourth course of oral methotrexate therapy was given without incident, and the patient remains in clinical and biochemical remission for 18 months following treatment.
CASE 1
CASE 2
Two patients with persistent partial molar pregnancy were successfully treated with oral methotrexate therapy. The advantages of this form of therapy are discussed. o 1~2ACAW PM, I~C.
M.G. was a 28-year-old white female, gravida 3 para N.A. was a twenty-two-year-old white female, gravida 2, 14 weeks pregnant by date, found to have an S-week 2 para 1, who presented to the emergency room as an 233 0090-8258l92 $4.00 Copyright 0 1992by AcademicPress,Inc. All rights of reproductionin any form reserved.
234
BRUCE PATSNER
incomplete spontaneous abortion at lo-weeks gestation. Products of conception from dilatation and curettage looked grossly normal but microscopically contained mild trophoblastic hyperplasia and mild hydropic villi as well as a fetal sac. Karyotype was not performed. Postevacuation uterine involution was normal, but irregular vaginal spotting persisted 4 weeks after evacuation and serum P-HCG was 7500 mIU/ml which rose to 9000 mIU/ml 1 week later. Chest X ray was normal as was general physical and pelvic examination. Oral contraception had been used since uterine evacuation. The diagnosis of persistent partial molar pregnancy was made after pelvic sonogram revealed no ectopic or intrauterine pregnancy. Oral methotrexate therapy, 25 mg/day for 5 days, with a planned 9-day window, was initiated. Serum /3-HCG fell rapidly to 200 mIU/ml after the first course and was less than 5 mIU/ml after the second course. No further therapy was offered, and the patient remains in clinical and biochemical remission 1 year after completing therapy. No hematologic, hepatic, gastrointestinal, or mucosal toxicity was noted during treatment. DISCUSSION Oral methotrexate therapy has been used to treat nonmetastatic GTD [8] following complete molar pregnancy, with success rates comparable to those obtained with more intensive intramuscular or intravenous methotrexate with leucovorin rescue regimens despite concerns about intestinal absorption of methotrexate. It is possible that some of the reported patients successfully treated with oral methotrexate for nonmetastatic GTD following evacuation of molar pregnancy may in fact have had partial moles. In addition to having a lower patient morbidity, oral
methotrexate is more convenient for the patient as well as less expensive. Gastrointestinal or mucosal toxicity was not a problem using the current dosage schedule, and patient compliance with this regimen was excellent. Because partial molar pregnancy less frequently results in GTD and is virtually never metastatic, its less aggressive biologic behavior compared to that of complete molar pregnancy makes it an excellent candidate for a less intensive but equally efficacious chemotherapy regimen. Oral methotrexate therapy should be considered for treatment of persistent GTD following evacuation of partial molar pregnancy because of its proven efficacy, cost effectiveness, ease of administration, and mild toxicity profile. REFERENCES 1. Szulman, A. E., and Surti, U. The clinicopathologic profile of the partial hydatidiform mole, Obstet. Gynecol. 59, 597-602 (1982). 2. Fine, C., Bundy, A. L., Berkowitz, R. S., et al. Sonographic diagnosis of partial hydatidiform mole, Obstet. Gynecol. 73, 414-418 (1989). 3. Berkowitz, R. S., Goldstein, D. P., and Bernstein, M. R. Partial molar pregnancy: A separate entity, Cont. Obstet. Gynecol. 6, 99102 (1988). 4. Stone, M., and Bagshawe, K. D. Hydatidiform mole: Two entities, Lancet 1, 535 (1976). 5. Berkowitz, R. S., Goldstein, D. P., and Bernstein, M. R. Natural history of partial molar pregnancy, Obstet. Gynecol. 66, 677-681 (1985). 6. Szulman, A. E., Ma, H. K., Wong, L. C., and Hsu, C. Residual trophoblastic disease in association with partial hydatidiform mole, Obstet. Gynecol. 57, 392-394 (1981). Appelman, Z., Dgani, R., Zalef, Y., Elchalal, U., and Caspi, B. Persistent gestational trophoblastic disease following evacuation of a tetraploid partial hydatidifonn mole, Gynecol. Oncol. 44, 101-103 (1992). Barter, J. F., Soong, S. J., Hatch, K. D., et al. Treatment of nonmetastatic gestational trophoblastic disease with oral methotrexate, Am. J. Obstet. Gynecol. 157, 1166-1168 (1987).
233-234 (1992)
CASE REPORT Successful Treatment of Persistent Partial Mole with Oral Methotrexate Therapy BRUCE PATSNER, New Jersey Gynecologic
Oncology,
P.A., Riverview
M.D.
Medical Center, Red Bank, New Jersey 07701
Received August 23, 1991
Partial molar pregnancy is a relatively indolent form of hydatidiform mole commonly characterized by the presence of a fetus, mild hydropic villous swelling, focal trophoblastic hyperplasia, and a triploid genetic component [l]. Patients with partial mole often present as missed or incomplete abortion. The diagnosis may be suggested preevacuation by the ultrasonographic findings of both cystic changes in the decidua or placenta and a ratio of transverse to anteroposterior diameter of the gestational sac of greater than 1.5 [2]. The risk of developing gestational trophoblastic disease (GTD) following evacuation of partial molar pregnancy is low and reported to be about 4% (range, O-11%) [3]. Virtually all cases of persistent partial mole after uterine evacuation have been confined to the uterus, although one case of metastatic disease has been reported [4]. Treatment of persistent partial molar pregnancy has been successful in all casesand has consisted of traditional intravenous methotrexate with leucovorin rescue [5]. Intramuscular bleomycin has also been reported [6] to be effective, as has intravenous actinomycin D [7]. Oral methotrexate therapy has not been previously reported for treatment of persistent partial molar pregnancy. The present report describes two cases of successful use of oral methotrexate therapy to treat persistent trophoblast following evacuation of a partial molar pregnancy.
intrauterine gestation by abdominal ultrasound obtained because of vaginal spotting. A singleton pregnancy without fetal heartbeat was noted, as was a large sonolucent area within the placenta. Serum P-HCG was 213,000 mIU/ml. Repeat examination 2 weeks later revealed an S-week-size uterus, and repeat scan confirmed fetal demise. Dilatation and curettage were performed and curettings read as partial molar pregnancy, triploid on karyotype. Uterine involution postevacuation was complete, but serum /3-HCG rose from 6000 to 8000 mIU/ml 6 to 8 weeks postevacuation. Chest X ray was normal. Repeat uterine sonogram revealed a complex density in the fundus, with an area of sonolucency. The diagnosis of persistent partial molar pregnancy was made and the patient referred for evaluation. Prior to initiating therapy, pelvic examination revealed a soft, 4-week size uterus and serum /3-HCG was 9600 mIU/ml. All serum blood chemistries and complete blood count were normal. Oral contraceptive therapy was initiated and oral methotrexate, 25 mg/day for 5 days, with a planned 9-day window, was started. Serum /3-HCG levels after each of three courses of oral methotrexate therapy were 2000, 390, and 5 mIU/ml. Pelvic examination was normal, as were blood counts and chemistries at all times. Two days of vaginal spotting occurred at the start of each course of oral methotrexate but no stomatitis, nausea, or vomiting occurred. A final fourth course of oral methotrexate therapy was given without incident, and the patient remains in clinical and biochemical remission for 18 months following treatment.
CASE 1
CASE 2
Two patients with persistent partial molar pregnancy were successfully treated with oral methotrexate therapy. The advantages of this form of therapy are discussed. o 1~2ACAW PM, I~C.
M.G. was a 28-year-old white female, gravida 3 para N.A. was a twenty-two-year-old white female, gravida 2, 14 weeks pregnant by date, found to have an S-week 2 para 1, who presented to the emergency room as an 233 0090-8258l92 $4.00 Copyright 0 1992by AcademicPress,Inc. All rights of reproductionin any form reserved.
234
BRUCE PATSNER
incomplete spontaneous abortion at lo-weeks gestation. Products of conception from dilatation and curettage looked grossly normal but microscopically contained mild trophoblastic hyperplasia and mild hydropic villi as well as a fetal sac. Karyotype was not performed. Postevacuation uterine involution was normal, but irregular vaginal spotting persisted 4 weeks after evacuation and serum P-HCG was 7500 mIU/ml which rose to 9000 mIU/ml 1 week later. Chest X ray was normal as was general physical and pelvic examination. Oral contraception had been used since uterine evacuation. The diagnosis of persistent partial molar pregnancy was made after pelvic sonogram revealed no ectopic or intrauterine pregnancy. Oral methotrexate therapy, 25 mg/day for 5 days, with a planned 9-day window, was initiated. Serum /3-HCG fell rapidly to 200 mIU/ml after the first course and was less than 5 mIU/ml after the second course. No further therapy was offered, and the patient remains in clinical and biochemical remission 1 year after completing therapy. No hematologic, hepatic, gastrointestinal, or mucosal toxicity was noted during treatment. DISCUSSION Oral methotrexate therapy has been used to treat nonmetastatic GTD [8] following complete molar pregnancy, with success rates comparable to those obtained with more intensive intramuscular or intravenous methotrexate with leucovorin rescue regimens despite concerns about intestinal absorption of methotrexate. It is possible that some of the reported patients successfully treated with oral methotrexate for nonmetastatic GTD following evacuation of molar pregnancy may in fact have had partial moles. In addition to having a lower patient morbidity, oral
methotrexate is more convenient for the patient as well as less expensive. Gastrointestinal or mucosal toxicity was not a problem using the current dosage schedule, and patient compliance with this regimen was excellent. Because partial molar pregnancy less frequently results in GTD and is virtually never metastatic, its less aggressive biologic behavior compared to that of complete molar pregnancy makes it an excellent candidate for a less intensive but equally efficacious chemotherapy regimen. Oral methotrexate therapy should be considered for treatment of persistent GTD following evacuation of partial molar pregnancy because of its proven efficacy, cost effectiveness, ease of administration, and mild toxicity profile. REFERENCES 1. Szulman, A. E., and Surti, U. The clinicopathologic profile of the partial hydatidiform mole, Obstet. Gynecol. 59, 597-602 (1982). 2. Fine, C., Bundy, A. L., Berkowitz, R. S., et al. Sonographic diagnosis of partial hydatidiform mole, Obstet. Gynecol. 73, 414-418 (1989). 3. Berkowitz, R. S., Goldstein, D. P., and Bernstein, M. R. Partial molar pregnancy: A separate entity, Cont. Obstet. Gynecol. 6, 99102 (1988). 4. Stone, M., and Bagshawe, K. D. Hydatidiform mole: Two entities, Lancet 1, 535 (1976). 5. Berkowitz, R. S., Goldstein, D. P., and Bernstein, M. R. Natural history of partial molar pregnancy, Obstet. Gynecol. 66, 677-681 (1985). 6. Szulman, A. E., Ma, H. K., Wong, L. C., and Hsu, C. Residual trophoblastic disease in association with partial hydatidiform mole, Obstet. Gynecol. 57, 392-394 (1981). Appelman, Z., Dgani, R., Zalef, Y., Elchalal, U., and Caspi, B. Persistent gestational trophoblastic disease following evacuation of a tetraploid partial hydatidifonn mole, Gynecol. Oncol. 44, 101-103 (1992). Barter, J. F., Soong, S. J., Hatch, K. D., et al. Treatment of nonmetastatic gestational trophoblastic disease with oral methotrexate, Am. J. Obstet. Gynecol. 157, 1166-1168 (1987).