Physiological tremor is suppressed and force steadiness is enhanced with increased availability of serotonin regardless of muscle fatigue.

Although there is evidence that 5-HT acts as an excitatory neuromodulator to enhance maximal force generation, it is largely unknown how 5-HT activity influences the ability to sustain a constant force during steady-state contractions. A total of 22 healthy individuals participated in the study, where elbow flexion force was assessed during brief isometric contractions at 10% maximal voluntary contraction (MVC), 60% MVC, MVC, and during a sustained MVC. The selective serotonin reuptake inhibitor, paroxetine, suppressed physiological tremor and increased force steadiness when performing the isometric contractions. In particular, a main effect of drug was detected for peak power of force within the 8-12 Hz range (P = 0.004) and the coefficient of variation (CV) of force (P < 0.001). A second experiment was performed where intermittent isometric elbow flexions (20% MVC sustained for 2 min) were repeatedly performed so that serotonergic effects on physiological tremor and force steadiness could be assessed during the development of fatigue. Main effects of drug were once again detected for peak power of force in the 8-12 Hz range (P = 0.002) and CV of force (P = 0.003), where paroxetine suppressed physiological tremor and increased force steadiness when the elbow flexors were fatigued. The findings of this study suggest that enhanced availability of 5-HT in humans has a profound influence of maintaining constant force during steady-state contractions. The action of 5-HT appears to suppress fluctuations in force regardless of the fatigue state of the muscle.NEW & NOTEWORTHY Converging lines of research indicate that enhanced serotonin availability increases maximal force generation. However, it is largely unknown how serotonin influences the ability to sustain a constant force. We performed two experiments to assess physiological tremor and force steadiness in unfatigued and fatigued muscle when serotonin availability was enhanced in the central nervous system. Enhanced availability of serotonin reduced physiological tremor amplitude and improved steadiness regardless of muscle fatigue.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

OBJECTIVE: To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. METHODS: Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). RESULTS: The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. CONCLUSIONS: The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors.

Recurrence patterns and prognosis of endometrial stromal sarcoma and the potential of tyrosine kinase-inhibiting therapy.

OBJECTIVE: Endometrial stromal sarcoma (ESS) is a rare uterine malignancy. The current treatment approaches yield unsatisfactory results, and potential therapeutic targets need exploration. METHODS: We reviewed the electronic medical records of 74 patients with low-grade ESS who had been evaluated at the University of Texas MD Anderson Cancer Center between 1995 and 2006. Using immunohistochemistry, we tested the expression of targets in paraffin-embedded tissue samples taken from 13 of the patients. RESULTS: Forty-seven patients (64%) had a recurrence, and 16 (22%) had died of their disease at last follow-up. The 10-year progression-free survival (PFS) rate was 43% (median PFS duration, 108months), and the overall survival (OS) rate was 85% (median OS, 288months). Patients who received hormonal therapy had an overall response rate of 27%; another 53% had stable disease, with a median time to progression of 24months. No complete response or partial response was observed among patients who received radiotherapy or chemotherapy. In the paraffin-embedded specimens we tested, c-abl was expressed universally. Expression of PDGF-α, PDGF-ß, VEGF, and c-Kit was detected in 33%, 36%, 54%, and 8%, of specimens, respectively. EGFR and HER-2 were not detectable in any specimens. CONCLUSIONS: Our study suggests that ESS is a hormone-dependent malignancy, with hormonal therapy having activity in recurrent disease. Targeted therapy, specifically targeting c-abl may be a potential treatment for this disease.

Chemotherapy for gynecological malignancies in organ transplantation patients: report of two cases.

Long-term risk of gynecological malignancies in organ transplantation patients has increased compared with that of the general population owing to the use of immunosuppressive agents. Treatment, especially chemotherapy, in these patients should take into consideration their renal function and the effects of immunosuppressive agents. We here present two case reports of patients with chemotherapy-treated gynecological malignancies who had previously received organ transplantation. The first case, a rare occurrence of simultaneous carcinomas of the uterine corpus and ovary, is the first such report in the English literature describing chemotherapy for concurrent serous papillary ovarian carcinoma and endometrioid endometrial carcinoma in a renal transplant patient. The second case report, describing chemotherapy for cervical cancer following two organ transplantation, also rare, is the first such report in the English literature and the first report of cervical cancer after heart-kidney transplantation.

Tamoxifen is safe and effective in gynecological cancer patients with renal dysfunction.

Tamoxifen has been found to be safe and effective in gynecological cancer patients with normal renal function. However, to our knowledge, no data exist regarding its effectiveness and toxicity in gynecological cancer patients with chronic kidney disease (CKD). Therefore, we retrospectively evaluated the effects of tamoxifen in patients with recurrent gynecological cancer and CKD. We collected clinical and demographic data for all patients. CKD was defined as a creatinine clearance (CrCl) level of less than 90 mL/min/1.73 m(2), in accordance with the National Kidney Foundation Kidney and Dialysis Outcomes Quality Initiative, and further categorized as mild, moderate, or severe (CrCl levels of 60-89, 30-59, and <30 mL/min/1.73 m(2), respectively). Twenty-nine patients were included in the study--22 with epithelial ovarian cancer, 4 with peritoneal cancer, and 3 with fallopian tube cancer. Thirteen patients had mild CKD, 13 had moderate, and 3 had severe. Most patients had been treated with 20 mg/day of tamoxifen every 4 weeks. The median duration of treatment was 5 months (range, 1-52 months). The overall complete response, partial response, stable disease, and disease progression rates were 0%, 10%, 41%, and 48%, respectively. Twenty-one percent of patients experienced hot flashes, and 7% experienced nausea. No major adverse reactions occurred. These findings were similar to those for gynecological cancer patients with normal renal function. In conclusion, 20 mg/day of tamoxifen is safe and effective in gynecological cancer patients with CKD.

Phase II multicenter open-label study of karenitecin in previously treated epithelial ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study.

The topoisomerase I agents are established as a therapy in recurrent ovarian cancer. Karenitecin, an analog of topotecan with solubility and pharmacologic advantages, was tested in a phase II trial in previously treated patients with recurrent or persistent ovarian cancer. The drug was administered intravenously over 1 h at a dose of 1.0 mg/m(2) daily for 5 days every 21 days. Patients were treated until disease progression, intolerable toxicity, or voluntary withdrawal. Response was evaluated according to modified RECIST criteria. Twenty-seven patients were entered into the study. One patient was inevaluable for not receiving any treatment. Of the 26 evaluable patients, there were two partial responses and one complete response for a total response rate of 12%. This response rate was insufficient to justify accrual to the second stage. The most common grade 3 or 4 toxicities were neutropenia (19%) and gastrointestinal (15%). Karenitecin is a well-tolerated topoisomerase compound but has minimal activity in extensively pretreated ovarian cancer with the dose-schedule employed.

Erosive osteoarthritis during treatment with bevacizumab and paclitaxel in a patient with recurrent papillary serous carcinoma of the ovary.

Bevacizumab (BVC) is currently used in recurrent ovarian cancer and as part of the initial treatment for ovarian cancer. The most serious toxicities associated with BVC include gastrointestinal perforations, delayed wound healing, and hemorrhage. Arthritis had never been addressed in patients who received BVC treatment. This is the first case report of arthritis emergence linked to BVC administration. A 59-year-old female with recurrent ovarian cancer received multiple hormonal and cytotoxic regimens for 5 years and then developed erosive osteoarthritis of the hands secondary to BVC and paclitaxel. This effect was confirmed by a significant improvement in her symptoms and signs, after treatment was discontinued.

Aromatase inhibitors in ovarian cancer: is there a role?

Estrogen plays a role in ovarian tumorigenesis. Aromatase is the enzyme required for the synthesis of estrogen via conversion of androgen to estrogen, which is the major source of estrogen in postmenopausal women. Aromatase is present in normal ovaries and other tissues (e.g., fat and muscle) as well as in 33-81% tumor tissues of ovarian cancer. Aromatase inhibitors (AIs) block estrogen synthesis by inhibiting aromatase activity. In patients with recurrent ovarian cancer, single-agent AI therapy has been shown to elicit clinical response rates of up to 35.7% and stable disease rates of 20-42%. Given the limited treatment options for recurrent ovarian cancer and the favorable safety profile and convenient use, AI is a rational option for prolonging platinum-free interval in recurrent ovarian cancer. Further studies are required to determine the efficacy of combination treatment with AIs and biological agents, determine the benefit of AIs for treating special types of ovarian cancer (e.g., endometrioid type), and identify biomarkers for targeted patient selection. This review summarizes the current epidemiologic, preclinical, and clinical data regarding estrogen's role in ovarian cancer, the expression and regulation of aromatase in this disease, the development and characteristics of the three generations of AIs, and the preclinical and clinical studies of AIs in the treatment of ovarian cancer.

Ovarian endometriosis associated with carcinoma and sarcoma: case report.

Endometriosis is a common clinical disorder that shares certain characteristics, metastasis and recurrence, with malignant neoplasms. Most malignant ovarian tumors arising from endometriosis are clear cell carcinoma or endometrioid adenocarcinoma. Few reports exist of sarcoma associated with endometriosis, and even fewer exist of multiple types of malignancies occurring simultaneously. Here, we report the case of a 32-year-old woman who presented with infertility and a pelvic mass. She underwent exploratory laparotomy and bilateral salpingo-oophorectomy. She was then referred to our institution for treatment recommendation. The pathologic findings revealed bilateral endometrioid adenofibroma of low malignant potential, which was associated with endometrioid intraepithelial carcinoma in the left ovary and high-grade sarcoma in the right ovary. Both tumors seemed to have arisen from endometriosis. She was treated with 75 mg/m2 of doxorubicin and 10 g/m2 of ifosfamide every three weeks for eight courses. She was later found to have bilateral brain metastases, which were resected and treated by whole-brain irradiation. She was again treated with doxorubicin and ifosfamide. The optimal treatment for endometriosis-associated ovarian cancer depends on the type of malignancy; simultaneously occurring multiple tumor types should be treated individually.

Clinical pharmacology, metabolism, and tissue distribution of 90Y-labeled monoclonal antibody B72.3 after intraperitoneal administration.

B72.3 is a murine monoclonal antibody that recognizes a high-molecular-weight tumor-associated glycoprotein (TAG-72). Nine patients with TAG-72-positive ovarian carcinoma or papillary serous carcinoma of the peritoneum received an intraperitoneal infusion of 2, 4, or 10 mg B72.3 labeled with 0.5-1.2 (mean, 0.8) mCi 90Y. All patients had laparotomy, with multiple tissue and tumor samples removed 3-7 days later. The concentration of the total 90Y label in peritoneal fluid cleared with an extrapolated half-life of 68.6 +/- 4.5 hours. A low-molecular-weight 90Y-labeled species of metabolite was identified by high-performance liquid chromatography. The concentration of this low-molecular-weight species initially increased in the peritoneal fluid, with a half-life of 0.9 hour, and was rapidly cleared from the peritoneal cavity, with a half-life of 23.1 hours. Both the 90Y-labeled metabolite and the 90Y-labeled B72.3 were absorbed into the plasma, with half-lives of 16 +/- 2.2 hours and 25 +/- 5 hours, respectively. The clearance half-lives for these agents in plasma were 25 +/- 3 hours for the metabolite and 42 +/- 17 hours for B72.3. Approximately 8%-11% of the total injected 90Y label appeared in urine over 72 hours. Most of the label (about 70%) was present as the 90Y-labeled metabolite, but about 30% of the 90Y label in urine appeared identical to the authentic 90Y-labeled B72.3 standard when assayed by chromatography. Tissue distribution studies showed that normal tumor tissue and omentum contained the highest content of 90Y (about 0.017% of the injected dose per gram), followed in descending order by liver, normal lymph nodes, peritoneum, bone, and fascia. The lowest concentrations of 90Y were found in rectus abdominis muscle, bone marrow, and fat. There was substantial heterogeneity in the uptake of the 90Y label into tumor sites among patients and among different sites within the same patient. No correlation could be demonstrated between the TAG-72 content and the amount of 90Y label found in tumor sites. Preliminary radiation dosimetry estimates suggest that the tumor sites received about 82.8 cGy for each millicurie of 90Y administered. Thus, if an adequate total radiation dose can be achieved, 90Y-labeled B72.3 should be therapeutically useful for treating diffuse intraperitoneal disease.

13-cis-retinoic acid plus interferon alpha-2a: highly active systemic therapy for squamous cell carcinoma of the cervix.

BACKGROUND: Chemotherapeutic study of cervical squamous cell carcinoma has shown some positive results. Complete plus partial (overall) response rates of 15%-35% (complete response rate, less than 5%) were achieved with the use of a small number of cytotoxic single agents in patients with advanced disease. In addition, overall response rates of 60%-70% (complete response rates, 10%-20%) were achieved with cisplatin-based, multiagent regimens in patients with primary, locally advanced disease. However, the lack of clear evidence that existing chemotherapy can achieve a survival benefit, coupled with the worldwide annual deaths of hundreds of thousands of women from cervical cancer, indicates the urgent need for effective systemic therapy for this disease. PURPOSE: In view of the preclinical and clinical evidence that supports testing of the novel combination of 13-cis-retinoic acid (13-cRA) plus interferon-alpha (IFN-alpha) in cervical squamous cell carcinoma, we conducted a phase II study of this regimen in locally advanced disease. METHODS: Twenty-six patients with untreated, locally advanced squamous cell carcinoma of the cervix were treated daily for at least 2 months with oral 13-cRA (1 mg/kg) and subcutaneous recombinant human IFN alpha-2a (6 million units). In 21 patients (81%), the disease was stage II or higher. RESULTS: Thirteen patients (50%) experienced major responses (tumor regression greater than or equal to 50%) in association with resolution of symptoms; one achieved complete response, and 12 experienced partial response. Seven with partial response are improving further, four are being maintained in partial response, and one responder has relapsed during therapy. The response rate is 58% (11 of 19) in patients with stage IIB or higher disease and 66% (10 of 15) in patients with bulky disease (at least one dimension greater than or equal to 10 cm). Of the 13 non-responders, nine have stable disease and four have had disease progression during therapy. Toxicity was minimal. CONCLUSION: These preliminary results indicate that systemic 13-cRA plus IFN alpha-2a is a highly active, well-tolerated therapy for locally advanced cervical cancer.

Allele loss at the c-Ha-ras1 locus in human ovarian cancer.

Recent reports have shown allele loss at the c-Ha-ras1 locus on the short arm of chromosome 11 in some types of tumors. To determine whether loss of heterozygosity occurs at the c-Ha-ras1 locus in uncultured human ovarian carcinomas we used Southern blot analysis to study DNA from 17 pairs of ovarian tumors and matched white blood cell samples from the same patients. In one of these 17 tumors, the c-Ha-ras1 locus was rearranged, and in five tumor DNAs from ten informative patients, a c-Ha-ras1 allele was lost. This loss, of relatively high incidence, appears to be an important characteristic of human ovarian cancer and may provide a useful tool for understanding its biological behavior.

Infiltration of interleukin-2-inducible killer cells in ascitic fluid and pleural effusions of advanced cancer patients.

Using ascitic fluid or pleural effusion obtained from 13 ovarian or metastatic breast cancer patients, we separated tumor cells from effusion-associated lymphocytes (EAL) with Percoll density centrifugation. Lymphocytes were incubated with recombinant interleukin 2 (IL-2) for 3-4 days and then assessed for tumoricidal activity in a 51chromium-release assay. The IL-2-activated EAL were found to lyse autologous fresh tumor cells, as well as allogeneic fresh tumor cells and FMEX tumor cells, a melanoma cell line which is resistant to natural killer cell activity but is sensitive to lysis by lymphokine-activated killer cells. There was little or no tumoricidal activity seen in freshly isolated EAL or in EAL which were cultured in medium without IL-2. Phenotypically, the IL-2-activated EAL were largely CD3-, although some cytolytic activity was found in CD3+ populations. Also, most activity was found in cells positive for CD2 (OKT11) and CD16 (Leu 11b), and negative for the monocyte marker Leu M3. These results indicate that the activated cell types found in EAL were predominantly natural killer/lymphokine-activated killer-like with a small contribution from T-cells. Finally, EAL were readily activated by IL-2 in medium containing autologous effusion fluid, indicating that in situ activation of tumoricidal activity by IL-2 can occur in the face of potentially inhibitory substances or cells that may exist in the effusions. Direct introduction of IL-2 may therefore be a potential therapeutic modality of effusion-forming cancers.

Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas.

Recently, tumor-specific allele loss has been shown to be an important characteristic of some tumors. When such loss includes one or more growth-regulatory genes, it may allow the expression of tumorigenicity. Using Southern blots, we analyzed normal and tumor DNA samples from 19 ovarian cancer patients, using a series of polymorphic DNA probes that map to a variety of chromosomal loci. Of 14 informative cases, tumor-specific allelic loss was observed in nine (64%) at the estrogen receptor (ESR) gene locus on chromosome 6q. On chromosome 17p at the D17S28 and D17S30 loci, allelic losses were also detected in 6 of 8 (75%) and 9 of 14 (64%) cases, respectively. Allelic loss at the HRAS1 gene locus on chromosome 11p occurred in 5 of 11 (46%) informative cases. The relatively high incidence of these allelic losses observed on chromosome 6q represents the first implication by molecular genetic analysis of this chromosomal region in a human malignancy, and it thus appears to be a genetic change specific to ovarian carcinoma. DNA sequence losses on 11p and 17p, also reported for other cancers, may reflect the presence of tumor- or growth-suppressor genes on these chromosomes that are important in the genesis of many tumor types, including ovarian malignancies.

Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro.

The aim of this study was to determine the antiproliferative activity of sodium phenylacetate (NaPa) against ovarian carcinoma cell lines. NaPa induced a dose-dependent inhibition (IC50 from 12 mM to >20 mM) of all ovarian carcinoma cell lines, although the sensitivity of individual lines to NaPa varied. Both cisplatin-sensitive and -resistant cell lines responded to NaPa, and growth-inhibitory activity was also detected against cells freshly isolated from malignant ascites of previously treated patients. The growth inhibitory effects that were produced by NaPa were time dependent, showing a maximum effect at 72 h, and were not associated with cytotoxic action. Growth inhibitory effects of NaPa were also reversible. After 48- and 72-h exposures to NaPa, a reduction in the percentage of cells in the S-phase was detected, with a concomitant recruitment of cells in the G0-G1 phase. Treatment with NaPa after different exposure times did not significantly increase the proportion of cells undergoing apoptosis. NaPa also produced a significant reduction in the percentage of cyclin-D1- and p21/ras-positive cells and in the percentage of cells positive for bcl-2, whereas the percentages of bax/p21-positive cells increased. NaPa produced minimal, if any, alterations of expression of HLA class I and transforming growth factor beta1 antigens. In contrast, the percentage of transforming growth factor beta2-positive cells decreased after exposure to NaPa. The combination of NaPa with cisplatin resulted in an additive inhibitory effect. Our results show, for the first time, that NaPa inhibits the growth of ovarian carcinoma cell lines and the cells from malignant ascites of chemotherapy-treated patients with ovarian carcinoma. The growth-inhibitory properties of NaPa suggest that this molecule could represent a prototype of a new class of compounds with possible therapeutic potential in patients with ovarian carcinoma.

Leuprolide acetate in the treatment of refractory or persistent epithelial ovarian cancer.

Leuprolide acetate (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered subcutaneously at a 1-mg dose for a minimum of 8 weeks to 23 patients with refractory epithelial ovarian cancer. Eighteen of these patients were evaluable. There were no complete responses. Four patients (17%) had a partial response, with a median duration of 52 weeks. Three of six patients with grade 1 carcinomas had a partial response and two had stabilized disease. There was only one response among 15 patients with grade 2 or 3 disease. Therapy was well tolerated, with three patients complaining of hot flashes and two of mild pedal edema. Leuprolide acetate thus shows evidence of antitumor activity against refractory grade 1 epithelial adenocarcinoma of the ovary. Further trials with larger numbers of patients should be conducted.

Combination chemotherapy for metastatic or recurrent adenocarcinoma of the cervix.

Twenty-four patients with recurrent or widespread adenocarcinoma of the cervix were treated with combination chemotherapy. The drugs used were 5-fluorouracil (5-FU) (500 to 800 mg/m2), doxorubicin (40 to 50 mg/m2), and cisplatin (50 to 60 mg/m2). The chemotherapy was administered as a 76-hour continuous infusion via a silastic central venous catheter and repeated every 28 days. The total response rate was 42% (25% complete and 17% partial). Median duration of response was 7 months. Areas of response were usually lung and lymph node metastases. Toxicity, mainly neutropenia, was acceptable. All patients relapsed. This combination chemotherapy results in a modest response rate for a malignancy about which there is little information regarding the treatment of disseminated disease. Future studies should determine the activity of this combination administered in a bolus fashion.

Paraneoplastic syndromes of gynecologic neoplasms.

PURPOSE AND DESIGN: The purpose of this review is to define and describe the paraneoplastic syndromes associated with gynecologic neoplasms. A comprehensive search of MEDLINE from 1966 to January 1996 and Cancerlit was performed. One hundred twenty-two reports were reviewed. RESULTS: Twenty-four paraneoplastic syndromes have been associated with gynecologic malignancies. Six anatomic systems are affected by these syndromes. However, except for disseminated intravascular coagulation and hypercalcemia, these syndromes are rare. CONCLUSION: Paraneoplastic syndromes are not frequently associated with gynecologic malignancies. The diagnosis of these syndromes is essential, as they can be occasionally life-threatening. Some paraneoplastic syndromes can be used as marker of progression or regression of the underlying malignancy.

Cisplatin therapy for disseminated mixed mesodermal sarcoma of the uterus.

Eighteen patients with metastatic mixed mesodermal sarcoma of the uterus received cisplatin therapy at the University of Texas (UT) M.D. Anderson Hospital and Tumor Institute at Houston. The dose of cisplatin varied from 75 mg/m2 to 100 mg/m2. Previous therapy included surgery in 11 patients, radiotherapy in two patients, and surgery plus radiotherapy in four patients. One patient had no prior therapy. Seven patients had also received prior chemotherapy with doxorubicin. Of 12 patients with measurable disease, one (8%) had a complete response and four (33%) had a partial response for an overall response rate of 42%. The median progression-free survival of patients treated with cisplatin as first- and second-line therapy was 4.5 and 5.5 months, respectively. Cisplatin demonstrated moderate activity with mild toxicity in this group of patients with metastatic mixed mesodermal uterine sarcomas. Further studies including cisplatin-containing combination regimens seem to be warranted.

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.