High dose rate (192)Ir afterloading brachytherapy for cancer of the vagina.

We report results of brachytherapy for carcinoma of the vagina, utilizing a Nucletron high dose rate system for Delclos Vaginal Applicators (cylinder) and Syed Template Applicators (interstitial). The linear quadratic (LQ) model was used to determine the optimum time-dose-fractionation schedules. Interstitial doses were determined at the isodose line that included gross tumour. Cylinder doses were determined either at the vaginal surface (5 cases), at 0.5 cm depth (5 cases), or at 1.0 cm depth (1 case). For the first treatment (n=19), interstitial templates were utilized in 8 patients and vaginal cylinders in 11. 11 patients received second treatments: 6 templates and 5 cylinders. The median dose of external beam radiation (n=15) was 40.0 Gy followed, after a median 23 day interval, by high dose rate brachytherapy (HDRB) of 4 fractions in 30-42 h; then a median interval gap of 25 days, followed by repeat HDRB. The median total fractionated HDRB dose per patient was 23.0 Gy (range: 6.9 Gy to 40.4 Gy; calculated low dose rate equivalent of 29.8 Gy). Tumour histologies included 14 squamous cell carcinomas, 2 adenocarcinomas, 2 melanomas, and 1 small cell tumour. Three patients experienced early brachytherapy-related complications (diarrhoea, dysuria and labial dermatitis). Three patients (15.8%) developed serious/late complications including ureteral stenosis, painful vaginal necrosis and small bowel obstruction. The first of these patients received 2 templates, the second a cylinder followed by a template and a cylinder, and the third a single cylinder. The 2 year progression-free survival was 39.3% (median 15.7 months), while the 2 year overall survival was 66.1% (median 29.9 months). (192)Ir afterloading HDRB is a feasible approach to women with vaginal cancer with acceptable toxicity and tumour response. Potential advantages include patient preference, outpatient cost-effectiveness in the case of cylinder technique, and no radiation exposure to hospital personnel. Long-term follow-up is needed to further assess late complications, and larger studies are needed to confirm our results.

Fatty acid composition of lysophosphatidic acid and lysophosphatidylinositol in plasma from patients with ovarian cancer and other gynecological diseases.

OBJECTIVE: We previously reported that plasma levels of total lysophosphatidic acid (LPA) represented a potential biomarker for ovarian cancer and other gynecological cancers [1]. However, total LPA is composed of different LPA species with distinct fatty acid chains. The major objective of the current study, therefore, was to determine whether one or more specific fatty acid LPA species was associated with disease or disease staging. If this was determined, these species could be useful in further improving the sensitivity and/or specificity of this biomarker for the diagnosis and/or prognosis of the disease. Because lysophosphatidylinositol (LPI) co-migrates with LPA, this study represents the analysis of combined molecular species from both lysolipid classes. METHODS: The patient population, sample collection, and analyses have been reported previously [1]. Lipids were hydrolyzed from the LPA band on thin-layer chromatography plates. The following individual fatty acid species were analyzed by gas chromatography: palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), arachidonic acid (20:4), and docosahexaenoic acid (22:6). The LPA/LPI fatty acid composition levels were analyzed and compared with disease status. RESULTS: Distinct plasma LPA/LPI fatty acid chain species were not associated with ovarian or other gynecological cancers, compared to patients with benign gynecological disease or healthy controls. However, an increased presence of unsaturated fatty acids in plasma LPA/LPI was found in patients with late-stage or recurrent ovarian cancer and possibly with other gynecological cancers. CONCLUSIONS: Analysis of individual fatty acid species present in plasma LPA/LPI do not appear to enhance the sensitivity or specificity of total LPA/LPI as a marker for gynecological cancer detection. However, our results suggest that increased LPA/LPI species with unsaturated fatty acid chains may be associated with late-stage or recurrent ovarian cancer.

The effect of radiation therapy on brain metastases from endometrial carcinoma: a retrospective study.

OBJECTIVE: The objective of this study was to investigate the effectiveness of radiation therapy as a treatment for brain metastases from endometrial carcinoma. METHODS: Between July 1985 and November 1999, 10 patients with brain metastases from endometrial carcinoma were treated at the Cleveland Clinic. We reviewed the patient and tumor characteristics at the time of the primary diagnosis and the brain metastases diagnosis. For the 8 patients who received radiation therapy with or without surgery, we analyzed the treatment results with regard to survival and local control of the metastases. RESULTS: Brain metastases from endometrial carcinoma were commonly accompanied by uncontrolled local-regional disease and systemic metastases. Multiple brain lesions developed in 7 of 10 patients. Two patients were treated with surgery alone and had a median survival of 2.75 months (4 and 1.5 months) after the brain metastases diagnosis. Three patients were treated with surgery and radiation therapy and lived for a median survival of 15 months (range 11.5 to 15.5 months). The 5 patients who were treated with radiation therapy without surgery had a median survival of 2.4 months (range 0.25 to 6 months). Patients with multiple brain metastases had a shorter survival than patients with a single metastasis. CONCLUSION: Overall survival after brain metastases development in patients with endometrial carcinoma was poor. Although the number of patients was small, radiation therapy alone resulted in poor survival. Combination treatment with surgery and radiation therapy may improve survival for selected patients.

Carboplatin skin testing: a skin-testing protocol for predicting hypersensitivity to carboplatin chemotherapy.

PURPOSE: A high incidence of moderate to severe hypersensitivity reactions (HRs) is noted in patients who have been treated with multiple courses of carboplatin. Presently, there is no reliable way to predict which patients may be at risk for this potentially severe adverse reaction. We developed a skin-test protocol to identify patients at high risk for HR to carboplatin chemotherapy. PATIENTS AND METHODS: Patients undergoing more than seven courses of carboplatin received a 0.02-mL intradermal injection of an undiluted aliquot of their planned carboplatin infusion 1 hour before each course of the agent. A positive skin test was prospectively defined as that resulting in a wheel of at least 5 mm with a surrounding flare. We recently reported a 27% incidence of HRs in patients receiving more than seven courses of carboplatin. These patients served as historical controls for the current study. RESULTS: Forty-seven patients with recurrent ovarian or primary peritoneal carcinoma receiving carboplatin were skin tested. Thirteen of 47 patients (28%) manifested a positive skin test at a median of nine total courses of carboplatin (range, eight to 17 courses). This rate of skin-test positivity was not significantly different from the incidence of documented HR reported in a historical control group (P =.89), suggesting comparable populations. A negative skin test accurately predicted the absence of HR in 166 of 168 courses of chemotherapy. Only two of 47 patients (4%) experienced a HR after a negative skin test. Thus, administering carboplatin only to patients with a negative skin test may result in a significant reduction in HRs relative to historical controls (P =.002). CONCLUSION: An easily performed skin test appears to predict patients in whom carboplatin may be safely administered. Treatment modifications based on the results of skin testing may reduce the incidence of HRs in patients receiving repeated courses of carboplatin.

Tumor distribution and survival in six patients with brain metastases from cervical carcinoma.

OBJECTIVE: The aim of this study was to investigate the patterns of brain involvement and the outcome of patients with brain metastases from cervical carcinoma. METHODS: Between January 1982 and November 1999, 1279 patients with brain metastases were treated at the Cleveland Clinic. Six of them had brain metastases from cervical carcinoma. We retrospectively reviewed the patient and tumor characteristics at the time of the primary diagnosis as well as at the time of the brain metastases diagnosis. RESULTS: Brain metastases from cervical carcinoma were rarely accompanied by systemic disease, but they were commonly accompanied by uncontrolled local-regional disease. The median interval from the appearance of the primary carcinoma to the detection of brain metastases in 5 patients was 12 months. Multiple brain lesions developed in 4 of 6 patients and consisted of multiple tumors distributed in the cerebral hemispheres (2 patients) or both the cerebral and the cerebellar hemispheres (2 patients). Only 2 patients had a single lesion confined to a cerebral hemisphere. One patient was treated with stereotactic radiosurgery alone, 3 with surgery followed by whole brain radiation therapy, 1 with whole brain radiotherapy, and 1 each with whole brain radiotherapy and stereotactic radiosurgery. Patients treated with surgery had a median survival of 8.25 months, while patients treated with whole brain radiotherapy with or without stereotactic radiosurgery had a median survival of 3.75 months. The 1 patient treated with stereotactic radiosurgery alone survived for 22.5 months. CONCLUSION: Although the number of the patients was too small to detect definitive patterns of brain metastases from cervical carcinoma, the results of our review suggest that, in contrast to previous reports, extended survival can occur with more aggressive treatment such as surgery or stereotactic radiosurgery.

The Society of Gynecologic Oncologists Outcomes Task Force. Study of endometrical cancer: initial experiences.

OBJECTIVE: The aim of this study was to develop an outcomes measure, which incorporates patient reported information, for The Society of Gynecologic Oncologists (SGO) to establish benchmarks in the treatment of endometrial cancer and demonstrate quality to third parties. METHODS: The Outcomes Task Force (OTF) developed an outcomes tool that included preoperative, intraoperative, and 120-day-postoperative assessments. Measures included demographics, patient-reported health status (SF36), comorbid conditions, living status, satisfaction surveys, operative events and disease characteristics. Patients (n = 297) were surveyed at 11 pilot sites from 10/1/97 to 9/1/99. RESULTS: The mean age of patients was 64.4 years and their mean Quetelet index was 33.2 kg/m(2). Forty-eight percent were Medicare beneficiaries and 25% were HMO patients. Mean comorbidity score was 19.1 (maximum possible 100). This represents approximately three comorbidities per average patient. Seventy-four percent were FIGO stage I, 9% stage II, 11% stage III, and 5% stage IV. Forty percent were FIGO grade 1, 35% grade 2, and 24% grade 3. Ninety-two percent of patients were able to live independently preoperatively and 91% were independent postoperatively. Seventy-seven percent of patients underwent total abdominal hysterectomy, 8% radical abdominal hysterectomy, 9% laparoscopic hysterectomy, and 1% vaginal hysterectomy. Mean length of stay was 3. 3 days and mean operative time was 119 min. Ninety-nine percent were staged and 80% underwent lymph node sampling. Two patients required unplanned returns to surgery and 8 required blood transfusion (27 units total). Postoperatively, 20% received radiation therapy and 13% received cytotoxic chemotherapy. Mean satisfaction score (scale 0 to 100) preoperatively was 86 and postoperative was 83. SF36 component summaries were preoperatively and 120 days postoperatively: physical component 43.6 vs 43.1; mental component 49.1 vs 50.6. CONCLUSION: The SGO has developed a tool for assessing outcomes for the treatment of endometrial cancer that can be made available to the membership to assess and objectively demonstrate quality of care to third parties.

Treatment of gynecologic cancers in pregnancy.

Gynecologic cancers are among the most common malignancies in reproductive-age women. Approximately 3% of women diagnosed with a malignancy of the reproductive tract will have a coexisting pregnancy. A pregnant woman with a gynecologic malignancy presents a significant challenge for the clinician for many reasons. Considerable diagnostic delay is common due to confusion of symptomatology with the physiologic changes associated with the pregnant state. The diagnostic options available for a patient suspected of having an invasive gynecologic malignancy may also be compromised by the pregnancy. In addition, difficult medical, ethical, and religious issues arise when the treatment of these malignancies is incompatible with continuation of the pregnancy. Unfortunately, a relatively limited experience with reproductive tract cancers in pregnancy has prevented the development of universally accepted management algorithms for many of the complex issues regarding their treatment. A literature review of diagnostic and treatment strategies for cervical, ovarian, endometrial, and vulvar carcinoma complicated by pregnancy is presented.

Treatment of relapsed carcinoma of the ovary with single-agent paclitaxel following exposure to paclitaxel and platinum employed as initial therapy.

OBJECTIVES: The aim of this study was to evaluate the ability of paclitaxel to achieve a second clinical response in patients with recurrent epithelial ovarian carcinoma who responded to standard therapy with platinum and paclitaxel in the initial setting. METHODS: Thirty-four patients with epithelial ovarian who demonstrated a complete response to paclitaxel and platinum in the initial treatment setting were retreated with paclitaxel as a single agent for relapse of their disease. Paclitaxel was given at a dose of 135-175 mg/m(2) over 3 h at 21-day intervals. Fifteen patients had platinum-resistant disease and 19 had potentially platinum-sensitive disease. Response was documented by physical examination, serial serum CA125 measurement, or radiologic evaluation. RESULTS: An objective response to paclitaxel retreatment was demonstrated in 15 patients (44%), with a median progression-free interval (PFI) of 8.6 months (range 4-17 months). An additional 14 patients (41%) demonstrated disease stabilization, with a median PFI of 7.4 months (range 3-13 months). Overall, retreatment with paclitaxel was well tolerated, with minimal cumulative toxicities, despite repetitive dosing. CONCLUSION: These results demonstrate that patients with ovarian cancer who relapse after initial treatment with paclitaxel often have disease that is still responsive to the agent. Given its relative lack of cumulative toxicity, retreatment with paclitaxel as a single agent is a reasonable therapeutic option for patients with recurrent ovarian cancer.

Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma.

PURPOSE: The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas. METHODS: Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion. RESULTS: The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction. CONCLUSIONS: Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

Evaluation of plasma lysophospholipids for diagnostic significance using electrospray ionization mass spectrometry (ESI-MS) analyses.

We previously reported that lysophosphatidic acid (LPA) represents a potential biomarker for ovarian and other gynecologic cancers. To further improve the accuracy and potentially increase the sensitivity and specificity of the assay, we developed an electrospray ionization mass spectrometry (ESI-MS)-based method to analyze LPA and related lysophospholipids. LPA, lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS), and lysophosphatidylcholine (LPC) could be detected with high sensitivity (in low pmol range) using this method. Standard curves were established for quantitative analysis. LPA and closely related lysophospholipids isolated from thin-layer chromatography (TLC) plates were analyzed directly by ESI-MS. This ESI-MS-based assay allows simultaneous detection and quantitation of all different species of LPAs and LPIs in a sample over a range of at least 5-300 pmol. Moreover, this test was at least 50 times more sensitive when a multiple reaction monitoring (MRM) mode was used. Using these protocols in a limited set of analysis, we found that both LPA and LPI were elevated in patients with ovarian cancer.

2-5A antisense directed against telomerase RNA produces apoptosis in ovarian cancer cells.

OBJECTIVE: RNase L is converted to an active form upon binding short 2',5'-oligoadenylates (2-5A). To direct RNase L to an RNA target, 2-5A is attached to an antisense oligonucleotide (2-5A antisense). This chimera can be directed against telomerase-an RNA-protein complex that elongates telomeric DNA and is involved in cellular immortalization. Our objective is to investigate the effect of 2-5A antisense by targeting telomerase RNA (hTR) in the ovarian cancer cell line, HEY-1B. METHODS: Baseline RNase L levels and telomerase activities were measured in both HEY-1B and normal ovarian epithelial cells (NOE). Cells were treated daily with chimeric oligonuclotides (ODN) directed against four different hTR sites, or control ODNs including nonchimeric antisense, 2-5A fused to a mismatched sequence, or inactive 2-5A fused to antisense. At 48 h, apoptosis was evaluated using the TUNEL assay. After six daily ODN administrations, telomerase activity was redetermined, and at 7 days viability counts were obtained. RESULTS: Both cell lines expressed similar levels of RNase L. Hey-1B displayed telomerase activity while NOE did not. After 7 days of transfection, 2-5A antisense ODNs caused profound cell death in the HEY-1B cells, but not in the NOE cells. This effect was seen regardless of hTR target site, and ODN controls showed no significant decrease in cell viability in either cell line. HEY1B cells treated with 2-5A antisense against hTR showed a decrease in telomerase activity and a profound induction of programmed cell death. CONCLUSIONS: The results suggest that 2-5A antisense directed against telomerase RNA results in apoptotic cell death in ovarian cancer cells, but not normal ovarian epithelial cells. The 2-5A antisense strategy may hold a considerable advantage over the conventional antisense approach in targeting cancer-causing genes.

Screening for gynecologic cancer.

Screening for cervical cancer with the Pap test has significantly reduced mortality from the disease. Although screening for ovarian and endometrial cancer is desirable, suggested strategies have not demonstrated efficacy. For the present time, educating patients with regard to the symptoms associated with these diseases and prompt evaluation of women who present with these symptoms helps limit unnecessary diagnostic delay.

Human papillomavirus typing and the reduction of cervical cancer risk.

Minor cervical cytologic abnormalities are common, but knowing which low-grade lesions will progress to cervical cancer--and therefore deserve biopsy and excision--is difficult. Since some human papillomavirus (HPV) types are strongly associated with cervical cancer, HPV typing may be a means of determining which patients with minor abnormalities require biopsy and treatment and which need only follow-up smears. This paper reviews the association between cervical cancer and HPV infection, the pathogenesis of HPV infection, the utility of HPV typing in training patients with a diagnosis of atypical squamous cells of undetermined significance, and the prospects for the development of an HPV vaccine.

The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. This regimen has thus far not been evaluated in UPSC. METHODS: Twenty-four patients with UPSC treated with platinum-based chemotherapy and paclitaxel were retrospectively evaluated. Eighteen patients received these agents in the adjuvant setting (n = 9) or for disease persistent after initial surgical management (n = 9). Eleven patients received one or more courses of this drug combination for recurrent disease, 5 of whom had prior exposure in the initial setting. RESULTS: Mean follow-up was 35 months (range 6-72+). A median progression-free interval (PFI) of 30 months (range 8-61+) was seen in patients treated in the adjuvant setting. Objective response, indicated by normalization of an elevated prechemotherapy CA125 level, was seen in 8 of 9 patients treated for residual disease after initial surgery (median PFI of 13 months, range 5-38+). Objective response of both measurable and/or evaluable disease was seen in 7 of 11 patients treated for recurrent disease (median PFI of 9 months, range 4-18). Six patients had retreatment with one or both agents and 4 responded a second time. Overall, the regimen was well tolerated. CONCLUSION: Paclitaxel and platinum-based chemotherapy has demonstrated activity in UPSC with acceptable toxicity. These results merit further investigation of the possible role of these agents in patients with this aggressive histologic subtype.

Survival probability in ovarian clear cell adenocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the 5-year survival probability (SP) of patients treated for ovarian clear cell adenocarcinoma (OCCA) at a single tertiary institution and to compare it to the 5-year SP of patients with other histologic subtypes of epithelial ovarian cancer. METHODS: Sixty-four patients with pure OCCA treated at the Cleveland Clinic Foundation from 1981 to 1996 were retrospectively identified and clinical information was abstracted. All histologic materials were reviewed by a single gynecologic pathologist. SP was calculated by the Kaplan-Meier method. SPs for OCCA patients were compared to that of other high-grade epithelial ovarian cancer patients in the gynecologic tumor registry. Cox proportional hazards modeling was used to identify varibles associated with decreased SP. RESULTS: The FIGO stages of OCCA study patients were Stage I, 31 (50%), Stage II, 6 (10%), Stage III, 17 (27%), and Stage IV, 8 (13%) (2 patients unstaged). Forty-four patients had no gross residual cancer at the completion of initial surgery while 9 patients had 1 cm residual. Forty-five (73%) received postoperative chemotherapy. The median follow-up for surviving patients is 97 months (range 38 to 209 months). The overall 5-year SP of OCCA patients is 50% with limited disease (Stages I and II) patients having a 5-year SP of 72% versus 17% 5-year SP in patients with advanced disease (P < 0.001). FIGO stage was most predictive of outcome. The overall 5-year SP of OCCA patients (50%) differed significantly (P < 0.05) from that of other ovarian cancer registry patients (30%). OCCA patients with limited cancer survived similarly to registry patients (72 vs 72%) as did patients with advanced OCCA compared with registry patients (17 vs 22%). CONCLUSIONS: When controlled for grade and stage, the overall survival with OCCA is identical to that of other high-grade epithelial ovarian cancers. Factors that account for the better overall survival of OCCA patients are more favorable disease stage, younger age, and improved debulking status.

Plasmacytoma of the ovary: a case report and literature review.

BACKGROUND: Ovarian plasmacytomas are a unique and unusual presentation of extramedullary plasmacytomas (EMP). A report of the seventh such case is presented with review of the previous six cases. METHODS: Surgical and medical staging were performed on the present case. The literature is reviewed. RESULTS: EMP involving the ovary is usually large at the time of presentation, more likely involving the left side, and without evidence of disseminated disease. As in other plasma cell dyscrasia, IgG paraprotein is more frequently involved. CONCLUSION: Adjuvant treatment for ovarian plasmacytomas is not clearly established; however, if complete surgical resection is achieved and no evidence of multiple myeloma is found, observation should be strongly considered.

Allelic imbalance on chromosome 17p13 in borderline (low malignant potential) epithelial ovarian tumors.

Borderline epithelial ovarian tumors (BEOTs) possess clinical and pathologic features intermediate between cystadenomas and cystadenocarcinomas. Although the clinical and pathologic characteristics of BEOTs are well described, the molecular aspects are poorly understood. Three regions of loss of heterozygosity (often referred to as allelic imbalance [AI] when identified by polymerase chain reaction) on chromosome 17p13, one of which includes the p53 gene, have been implicated in the development of ovarian and breast cancers. To provide evidence that genes in these regions also may be involved in the development of BEOTs, we undertook a detailed analysis of AI at all three loci in BEOTs from 21 patients. Seventeen of the BEOTs were serous and four were mucinous. Five of 21 tumors (24%) had AI at one or more loci. Four tumors had AI using the D17S695 marker, two of which showed AI only at this locus. In addition, three tumors exhibited AI at the D17S654 locus, one of which showed AI only at this locus. These data suggest that there may be two tumor suppressor genes distal to p53 involved in the development of at least a subset of BEOTs. Peritoneal implants from a subset of serous BEOTs also were evaluated for AI and were found to be concordant with the primary tumor in all cases. Their genetic similarity is consistent with the implantation theory of peritoneal spread of serous BEOTs in these cases.

Experience with platinum-paclitaxel chemotherapy in the initial management of papillary serous carcinoma of the peritoneum.

OBJECTIVE: The objective of this study was to assess the activity and toxicity of combination platinum-paclitaxel chemotherapy in the initial management of patients with papillary serous carcinoma of the peritoneum (PSCP). METHODS: Patients initially treated at The Cleveland Clinic Foundation (CCF) for PSCP with platinum-paclitaxel combination chemotherapy regimens were identified and clinical information was abstracted by chart review. Toxicity data, progression-free survival, and overall survival were determined. RESULTS: Thirty-eight patients (36 Stage IIIC and 2 Stage IV) were identified. All chemotherapy was administered as outpatient infusions. All patients received paclitaxel (135 or 175 mg/m2) and 12 received cisplatin and 26 carboplatin. Two hundred thirty-two cycles were administered, with only three (1.3%) episodes of grade 3 toxicity and no grade 4 toxicity. Ninety-two percent of patients experienced at least a 50% reduction in their CA-125 levels and 55% experienced a greater than 90% reduction. Median progression-free survival (Kaplan-Meier) was 15 months and median overall survival was 40 months. Survival for optimally debulked patients (median not yet reached with median follow-up of 24 months) was significantly better than for suboptimally debulked patients (median 32.8 months) (P = 0.012). CONCLUSION: Platinum-paclitaxel chemotherapy regimens have substantial utility in the initial management of PSCP patients. The toxicity profile is modest. Carboplatin or cisplatin in conjunction with paclitaxel is the current first-line recommended chemotherapy for PSCP.

Analysis of allelic imbalance on chromosome 17p13 in stage I and stage II epithelial ovarian cancers.

OBJECTIVES: To determine whether there is evidence for allelic imbalance (AI) on chromosome 17p13 in early-stage epithelial ovarian tumors. METHODS: Studies of allelic imbalance were performed on 29 stage I or stage II epithelial ovarian cancers using 5 short tandem repeat polymorphic markers (STRPs) on chromosome 17p13 by polymerase chain reaction (PCR) amplification. RESULTS: Sixteen of 29 (55%) tumors showed AI at one or more loci, including 7 of 29 (24%) tumors that showed distinct regions of AI. AI at p53 was present in only 9 of 25 (36%) informative tumors. A region of AI, defined by marker D17S654, close to candidate genes OVCA1 and OVCA2, was identified distal to p53 and occurred in 11 of 23 (48%) informative tumors. This region of AI also extended more distal to this locus, and included marker D17S695 where AI occurred in 11 of 26 (42%) informative tumors. Microsatellite instability was observed in 2 of 29 tumors. CONCLUSIONS: This study supports the presence of at least one tumor suppressor gene on chromosome 17p13 distal to p53 that is involved in the early development of epithelial ovarian cancer. This study also suggests that the molecular analysis of early-stage epithelial ovarian cancers can provide important information on the genetic etiology of ovarian cancers.