Progestogen treatment options for early endometrial cancer.

OBJECTIVE: Premenopausal women with early endometrial cancer may wish to maintain their fertility, and for some patients non-surgical treatment options may be attractive. We have examined our own experience with such patients, as there are limited published data so far to support clear guidelines in this area. DESIGN: Retrospective analysis of a case series. SETTING: Case series from a specialist gynaecological oncology unit in a major tertiary referral hospital. SAMPLE: Sixteen patients receiving progestogen therapy for stage-1 endometrial cancer. METHODS: We reviewed our experience of all patients receiving progestogen therapy for stage-1 endometrial cancer, and we particularly examined their cancer-free outcome and fertility potential. MAIN OUTCOME MEASURES: Response to treatment, duration of response, and subsequent pregnancies. RESULTS: Of the 16 patients investigated, four received an oral progestogen, five received the levonorgestrel-releasing intrauterine system (Mirena), and seven received both forms of treatment. Ten patients (63%) responded to treatment, with a median time to response of 5.5 months. Six patients did not respond to treatment, but all were either early in treatment or opted for surgical management before the average time of response. No patient who responded had a later recurrence. The mean total follow-up time was 27 months (range 3-134 months), with no patient deaths. Three patients had successful pregnancies, with one patient having two children. CONCLUSIONS: This form of treatment appears to be a realistic treatment option in selected patients in the closely supervised environment of a specialist gynaecological oncology unit.

Prognostic factors for recurrence in patients with FIGO stage I and II, intermediate or high risk endometrial cancer.

BACKGROUND: The aim of this study was to determine predictors for loco-regional or distant recurrence of disease in a subgroup of intermediate or high risk stage I and II endometrial cancer. METHODS: A retrospective analysis of 295 patients with histopathological stage I and II, intermediate or high risk endometrial cancer is reported. The following factors were studied: stage, grade, age, histologic diagnosis, lymphadenectomy, lymphovascular space invasion, and adjuvant radiotherapy. The Log-Rank test was used for statistical analyses and the Kaplan-Meyer method was used for time-to-event analysis. Multivariate analysis was also performed. RESULTS: Thirty-four (11.5%) patients developed a recurrence; 20 (59%) developed loco-regional recurrence, and 14 (41%) developed distant recurrence. In 20 women (59%), recurrence appeared within 3 years of surgery, and the actuarial survival at 3 years after recurrence was 29%. Multivariate analysis showed that for recurrence, age >60 years was a significant unfavourable prognostic factor (p < 0.05). CONCLUSIONS: We found low rates of recurrence in patients with early stage intermediate or high risk endometrial cancer. Only age was identified as an independent significant predictor for recurrence.

Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood progenitor cell support in previously untreated ovarian cancer: results of a Phase I study.

OBJECTIVE: In view of the significant activity of topotecan in ovarian cancer with dose-limiting toxicity (DLT) of myelosuppression, we evaluated the addition of topotecan to carboplatin and paclitaxel with peripheral blood progenitor cell (PBPC) support. METHODS: Patients with previously untreated stage IIIC or IV ovarian cancer with macroscopic residual disease following primary debulking surgery were eligible. Patients received two cycles of carboplatin AUC = 5 and 175 mg/m(2) of paclitaxel with collection of PBPCs after the second cycle. Patients subsequently received three cycles of high-dose therapy (HDT) with topotecan on a daily x5 schedule, paclitaxel (250 mg/m(2) over 24 h), and carboplatin (AUC = 12-16). RESULTS: Nineteen patients with a median age of 49 years (range 21-63) were enrolled and topotecan was escalated in 6 patient cohorts up to a dose of 4.5 mg/m(2)/day. Fifty-two of the planned 57 treatment cycles were delivered with no treatment-related deaths. Neutrophil and platelet recovery was rapid and the interval between HDT was 28 days. Febrile neutropenia occurred following 57% of all HDT cycles. DLTs of mucositis and diarrhea were observed at topotecan (4.5 mg/m(2)/day), paclitaxel (250 mg/m(2)) and carboplatin (AUC = 12). The protocol was subsequently modified to administer topotecan (2.5 mg/m(2)/day) with carboplatin (AUC = 16); however, 2 patients developed grade 4 diarrhea (1 with grade 3 mucositis and 1 with grade 4 mucositis). The clinical CR rate was 73% (14/19) with an overall clinical response rate of 95% (18/19). Of the 14 patients with a CCR, 13 of these underwent a second-look laparotomy with 8 (61%) achieving a pathological CR. With a median follow-up of 28 months (range 11-40 months), the median PFS is 36 months and OS has not been reached. CONCLUSION: When combined with carboplatin (AUC = 12) and paclitaxel (250 mg/m(2)), the recommended topotecan dose is 3.5 mg/m(2)/day for 5 days. This outpatient HDT regimen combines three of the most active drugs in ovarian cancer with acceptable toxicity and promising activity.

Primary malignant mixed Müllerian tumor of the vagina.

A 74-year-old woman presented with postmenopausal bleeding. Examination showed a 5.5-cm ulcerated, partly necrotic vaginal polyp arising anteriorly near the hymenal ring. Histology showed a malignant mixed Müllerian tumor (MMMT) with squamous and glandular epithelial and undifferentiated spindle cell stromal components, cytological atypia, and frequent mitoses. The tumor was closely associated with overlying vaginal intraepithelial neoplasia, grade III, from which it appeared to be arising. The patient was treated by surgical excision, followed by radiotherapy. Six months later, she developed a left supraclavicular lymph node metastasis. MMMT is a rare primary vaginal neoplasm, but, including this case, there have been at least 7 cases reported in the English language literature.

Integrated multimodality therapy for embryonal rhabdomyosarcoma of the lower genital tract in postpubertal females.

Embryonal rhabdomyosarcoma of the female lower genital tract is generally regarded as a neoplasm occurring in childhood, but has also been reported in adults. The philosophy of therapy, largely based on data obtained from pediatric patients, has evolved slowly from ultraradical surgery, without adjuvant therapy, to neoadjuvant chemotherapy followed by less radical surgery and postoperative radiation. We report here three cases of lower genital tract rhabdomyosarcoma in postpubertal females. A failure to observe complete responses from any single treatment modality suggests that for embryonal rhabdomyosarcoma in adult and adolescent women a multimodality approach to therapy is essential.

Pseudosinusoidal fetal heart rate pattern and fetal anaemia: case report and review.

The association of a pseudosinusoidal fetal heart rate pattern with fetal anaemia is reported. A system of classifying this cardiotocographic feature as minor, intermediate or major is discussed. The clinical correlates of each of these gradings and the differentiation from a true sinusoidal fetal heart rate pattern are presented.