Carboplatin chemotherapy in a pregnant patient with undifferentiated ovarian carcinoma: case report and review of the literature
Tsutomu Tabata, MD, Department of Obstetrics and Gynecology, Mie University School of Medicine, 2-174, Edobashi, Mie 514-8507, Japan. Email: firstname.lastname@example.org
There are already 12 reports of women treated by chemotherapy for epithelial ovarian cancer during pregnancy. However, most cases received chemotherapy of single cisplatin or cisplatin-based regime, and only four cases received carboplatin-containing chemotherapy. We report the case of a woman treated with single-agent carboplatin during pregnancy. The patient underwent bilateral salpingo-oophorectomy at 18 weeks of gestation and was diagnosed as having stage IC undifferentiated ovarian carcinoma. She was treated with four courses of carboplatin (area under the curve = 6.0) chemotherapy during pregnancy without severe toxicity. At 33 weeks of gestation, cesarean section was performed, followed by total hysterectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. No residual disease was histologically shown. The patient underwent additional chemotherapy with carboplatin and paclitaxel. After one year of follow-up, the baby shows normal growth and the patient has no evidence of disease. Postponing the termination of pregnancy by single-agent carboplatin chemotherapy during pregnancy might be considered as an option for therapy in selected women with ovarian malignancies.
Ovarian carcinoma during pregnancy remains a rare event. If termination of pregnancy can be postponed by the administration of chemotherapy during pregnancy without significant side effect to the fetus until the fetus reaches mature state, this treatment might be beneficial for both mother and child. In 1986, Malone et al.(1) first reported successful treatment of ovarian malignancy during pregnancy with multiagent chemotherapy. They achieved a good outcome for both mother and child.
There are already 12 reports of women who have received platinum-based chemotherapy for epithelial ovarian cancer during pregnancy(2–13). However, most cases received chemotherapy of single cisplatin or cisplatin-based regime, and only four cases received carboplatin-containing chemotherapy(2–5). We recently experienced the fifth case who received chemotherapy of single-agent carboplatin during pregnancy. It should be shared more widely to improve the prognosis of ovarian malignancy during pregnancy.
A 34-year-old nulliparous woman visited to her local obstetrician at 5 weeks of gestation. She had achieved a spontaneous pregnancy after a history of 12 years of infertility. Pelvic ultrasound revealed a single intrauterine gestational sac and a 5.2 × 4.6 cm solid right adnexal mass, but it could not detect the left ovary. Laboratory data revealed that she had gestational diabetes with a fasting plasma glucose of 180 mg/dL and HbA1c of 6.9%. The CA125 level was 317 U/mL. She was admitted to our hospital to control her plasma glucose level at 9 weeks of gestation. Glucose levels were controlled with insulin, and gradually decreased to the normal range after 1 month. At 16 weeks of gestation, the CA125 level elevated to 1045 U/mL and pelvic magnetic resonance imaging suggested ovarian malignancy because she had bilateral solid adnexal masses. At 18 weeks of gestation, she underwent exploratory laparotomy, which revealed an 8-cm right ovarian mass and a 4-cm left ovarian mass with papillary growth on the surface. Bilateral salpingo-oophorectomy and peritoneal washing cytology were performed. There was macroscopically no peritoneal implant in abdominal cavity. The final histopathologic diagnosis was undifferentiated carcinoma of the bilateral ovaries and peritoneal cytology was positive. The patient was stage IC according to FIGO classification. The patient and her family strongly desired continuation of the pregnancy. After extensive discussion, written informed consent was obtained to start chemotherapy during pregnancy so as to delay radical surgery until the fetus reaches maturity to adopt extrauterine life.
She underwent four courses of chemotherapy with carboplatin (area under the curve [AUC] = 6.0) from 21 to 33 weeks of gestation. The 5-HT3 antagonist was used before chemotherapy, and then there was no episode of nausea or vomiting. The patient tolerated the chemotherapy well and did not develop hematologic toxicity. The CA125 level decreased from 329 U/mL at the start of chemotherapy to 28 U/mL at the fifth course. Periodic obstetric ultrasound revealed appropriate fetal growth for gestational age.
At 33 weeks of gestation, cesarean section was performed, followed by total hysterectomy, total omentectomy, and pelvic and para-aortic lymphadenectomy. The final histopathologic diagnosis was negative for cancer. Her child was a male infant weighing 2222 g with an Apgar Score of 9 at 1 min and 10 at 5 min. Hematologic examination of cord blood was all within the normal range for fetal blood. After delivery, the patient underwent five courses of carboplatin (AUC = 6) and paclitaxel (175 mg/m2) as a 3-h infusion every 3 weeks. One year after the completion of treatment, the patient showed no evidence of disease and her son was normal.
The detection of malignancy requiring radical treatment during pregnancy often requires difficult decision regarding maternal therapy and the side effect of the therapy to the unborn child. The standard treatment for advanced ovarian cancer is debulking surgery and hysterectomy followed by adjuvant chemotherapy. However, administering chemotherapy to delay the surgical treatment until fetal maturity is reached was considered, and 22 cases have been reported (Table 1)(1–22).
Table 1. Clinical characteristics of cases administered chemotherapy for malignant ovarian tumor during pregnancy
|Number of patients||13||9|
|Age (years) (mean) (range)||34 (22–43)||24 (18–29)|
|Gestational age at diagnosis|
| First trimester||7||2|
| Second trimester||6||7|
|Gestational age at operation|
| First trimester||1||1|
| Second trimester||12||7|
| Unknown|| ||1|
|Gestational age at chemotherapy|
| First trimester||0||0|
| Second trimester||13||9|
| Platinum containing||13||6(1, 14–18)|
|Gestational age at delivery (weeks) (mean) (range)||35 (30–37)||35 (28–39)|
| I (number of recurrent patients)||3 (0)||5 (0)|
| II–IV (number of recurrent patients)||7 (2)||2 (1)|
| Unknown stage (number of recurrent patients)||3 (0)||2 (0)|
|Duration of follow-up (years) (mean) (range)||19 (5–36)b||17 (0.3–52)c|
In pregnant patients with ovarian malignancy, termination of the pregnancy during the first trimester and prompt treatment to maximize the probability of cure are usually recommended. However, even if an ovarian mass is detected during the first trimester, surgery has been avoided until the second trimester(2,7,8,10,13,14). Indeed, both patient and physician did not choose an operation in the first trimester because of the risk of fetal damage or abortion due to laparotomy. Table 1 shows that nine patients had ovarian tumors detected in the first trimester, but only two patients underwent surgery during the same trimester. One patient was performed an operation in the first trimester because of signs of ovarian torsion(4), and the other patient underwent left salpingo-oophorectomy at 13 weeks of gestation after detection of an ovarian tumor at 7 weeks(21). Accordingly, most pregnant women with ovarian tumors detected in the first trimester postponed surgery until the second trimester, except in emergency situations like ovarian torsion.
Copeland et al.(22) reviewed the literature on malignant ovarian tumors during pregnancy, and they concluded that 45% are germ cell tumors and 37.5% are epithelial tumors. For malignant germ cell tumors in patients who desire a baby, conservative surgery such as unilateral salpingo-oophorectomy may sometimes be selected even if the disease is advanced, because there is effective chemotherapy for these tumors. If the fetus can tolerate chemotherapy for germ cell tumors, the possibility of performing chemotherapy during pregnancy to postpone delivery and surgery until fetal maturity has been reached is clinically relevant in patients with chemotherapy-sensitive ovarian cancer. Most serous or endometrioid ovarian cancers are sensitive to chemotherapy, but clear cell or mucinous carcinoma may not respond to chemotherapy during pregnancy because of the resistance of these tumors.
Chemotherapy plays an important role in the treatment of ovarian malignancies, but potential toxicity for the developing fetus must be considered. All chemotherapy agents are theoretically teratogenic. The standard adjuvant regimen for epithelial ovarian cancer is carboplatin and paclitaxel. As far as the range of chemotherapy agents is concerned, monotherapy with carboplatin was chosen for present case in order to avoid nausea and vomiting, since the patient required careful glycemic control because of her gestational diabetes. There are previously four reports of the patients who have received carboplatin-containing chemotherapy for epithelial ovarian cancer during pregnancy, and these four cases had no complications(2–5). In one of four cases, however, the regime of chemotherapy was changed from cisplatin-containing chemotherapy to carboplatin-containing one, because maternal ototoxicity was documented after two cycles of initial cisplatin-containing chemotherapy. Paclitaxel was excluded because there was insufficient experience with the use of taxanes during pregnancy. There have been only two papers published about paclitaxel-containing chemotherapy for ovarian cancer during pregnancy. Platinum-based chemotherapy has been reported to be generally well tolerated during pregnancy.
Among all of the cases published to date, only three recurrences after chemotherapy during pregnancy have been reported. One was recurrent endodermal sinus tumor and two were stage IIIC serous adenocarcinoma(9,11,19). In early-stage cases, it seems that treatment can be temporized for the good of the fetus without the maternal poor prognosis(1,10,14,21). However, there might have been a bias because only the case with successful outcome was reported.
If a patient with an early ovarian malignancy strongly desires to continue her pregnancy, the use of chemotherapy during the second trimester to postpone surgery until fetal maturity might be considered, except for chemoresistant ovarian malignancies. It is still controversial whether chemotherapy can be used during pregnancy to postpone delivery in patients who have more advanced disease. It is mandatory to accumulate cases with chemotherapy of ovarian malignancy during pregnancy, before the guideline for the treatment of pregnant women with ovarian malignancy will be established.