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Cerebral metastasis from a primary adenocarcinoma of the fallopian tube.

BACKGROUND: Primary adenocarcinoma of the fallopian tube is a rare disease, and cerebral metastasis from this tumor is an extremely rare event. CASE: A 61-year-old female, who had been thought to be in a disease-free state after the initial treatment for stage IIIc fallopian tube adenocarcinoma, presented with severe headache, dizziness, nausea, and vomiting. Brain CT and MRI revealed solitary metastatic lesion in the cerebrum, which was the only site of recurrence. It was removed surgically, followed by platinum-based combination chemotherapy, and a clinical remission was achieved for 36 months. CONCLUSION: Attention should be paid to the possibility of cerebral metastasis in patients who develop neurogenic signs and symptoms. Prolonged survival could be achieved with aggressive treatment containing surgical debulking and adjuvant chemotherapy for solitary cerebral metastasis.

Adenocarcinoma↗

Preoperative evaluation of pelvic tumors by Doppler and three-dimensional sonography.

OBJECTIVE: To study a spectrum of systems (two-dimensional transvaginal, transvaginal color Doppler, three-dimensional, three-dimensional power Doppler, and contrast-enhanced three-dimensional power Doppler sonography) for preoperative evaluation of pelvic tumors. METHODS: Two hundred ninety-two patients were evaluated by the 5 complementary methods in preoperative sonographic assessments. We examined adnexal and endometrial morphology, thickness, and volume by two- and three-dimensional sonography and analyzed blood flow by transvaginal color, pulsed Doppler, and three-dimensional power Doppler sonography in all examined patients. In 89 patients with complex adnexal lesions of uncertain malignancy, contrast-enhanced three-dimensional power Doppler sonography was performed. RESULTS: Morphologic assessment by three-dimensional sonography yielded additional information in 58% of cases compared with two-dimensional sonography. Furthermore, this modality was superior to two-dimensional sonography in accurate depiction and diagnosis of 2 cases of fallopian tube carcinoma. Combined morphology and vascular indexing reached sensitivity of 97% and specificity of 99%. Endometrial volume in patients with malignant disease was significantly different (28.2 +/- 0.02 cm3) from that in those who had hyperplasia (7.81 +/- 0.03 cm3), polyps (3.5 +/- 0.02 cm3), or normal endometria (0.8 +/- 0.02 cm3). With combined morphologic and three-dimensional power Doppler examination of endometrial lesions, sensitivity and specificity reached 89% and 97%, respectively. CONCLUSIONS: Combined morphologic and vascular imaging improves preoperative assessment of gynecologic tumors.

Adult↗

Primary clear cell adenocarcinoma of the fallopian tube with brain metastasis: a case report.

The first reported case of cerebellar metastasis from primary clear cell adenocarcinoma of the fallopian tube is presented. Initially diagnosed as stage Ia, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy, followed by cisplatin-based chemotherapy and whole pelvic irradiation. Thirty six months later multiple pulmonary metastases were detected that did not respond to chemotherapy. Later the patient presented with cerebellar metastasis. She received whole brain radiotherapy and steroids. The brain lesion partially responded and the patient's neurologic symptoms improved. Throughout there was no evidence of local recurrence. This case suggests that with the prolonged survival achieved by aggressive treatment occult brain metastases might become apparent.

Adenocarcinoma, Clear Cell↗

DNA ploidy in primary fallopian-tube carcinoma using image cytometry.

Determination of DNA ploidy in 61 samples of primary Fallopian-tube carcinoma (FTC) by use of image cytometry is presented. Of these samples, 48 showed an aneuploid DNA content. Patients with euploid DNA content showed a median survival time of 33.8 months compared to 24.5 months for aneuploid cases. A high incidence of aneuploid tumors was consistently observed among all FIGO stages and in all groups of histologic grading. However, no correlation between ploidy and FIGO stage or histologic grading could be demonstrated. This observation could be regarded as a marker for the high aggressiveness of FTC which has been repeatedly described in the past.

Adult↗

Brain metastases from a primary carcinoma of the fallopian tube.

Central nervous system involvement by gynecological tumors is considered an uncommon event. Among 47 patients registered for tubal carcinoma in our institution between 1982 and 1994, 3 (6.4%) developed brain metastases. The median age at the time of the diagnosis of central nervous system metastases was 61 years. The median interval between diagnosis of tubal cancer and documentation of brain involvement was 37 months. All deposits were diagnosed as contrast-enhancing, space-occupying lesions on computed tomography scans. Two patients had cerebral metastases, 1 had cerebellar involvement. The central nervous system was the only site of recurrent disease in 1 patient 37 months after diagnosis of tubal carcinoma. The median survival from diagnosis of brain metastases was 1 month. Attention should be paid to the possibility of distant metastases associated with tubal carcinoma in order to treat these patients promptly.

Adenocarcinoma↗

Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract.

AIM: To investigate serum placental-type alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. METHODS: PLAP-type immunoreactivity was measured in 180 women with non-ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube cancers. RESULTS: Serum PLAP-type activities were no different from controls in patients with squamous cell tumours. Women with adenocarcinoma of the cervix, endometrium, and fallopian tube had increased values: women with endometrial cancer had a median value nearly four times greater than that of controls. There was no direct correlation between PLAP-type activities and stage of disease in patients with endometrial cancer, but values reverted to normal after treatment. CONCLUSIONS: Serum PLAP-type measurements are of no value in the management of patients with squamous cell tumours of the female reproductive tract. Raised activities can, however, be found in glandular tumours, in particular endometrial cancer where serum PLAP-type measurements may be of value in predicting remission.

Adenocarcinoma↗

[Platin-containing cytostatic combinations in the therapy of advanced gynecologic carcinomas].

95 patients with advanced and recurred gynecological carcinomas (57 ovarian carcinoma, 22 cervical carcinoma) were treated by a platinum (CDDP) based polychemotherapy platinum, adriamycine, cyclophosphamide (PAC); platinum, adriamycine, bleomycine (PAB), 22 out of 48 patients with low differentiated epithelial carcinoma of the ovary stage III and IV achieved a remission (13 CR; 9 PR). Today 6 of the CR-patients survive 23 months without recurrence; 7 had a medium survival of 17 months. Medium survival of PR-patients was 15 months. 6 NED-patients survive 22 months without recurrence and 2 NED-patients died after 19,5 months. The overall response rate (CR, PR, NED) was 63%. A retrospective comparison with 78 patients (low differentiated ovarian carcinoma stage III and IV) treated by a cyclophosphamide monotherapy shows an elevated 2-year survival rate of the PAC treated patients. The other patients suffered from carcinoma of the mamma, the tubes, the corpus uteri, the vagina, and the vulva. The therapeutic effect of CDDP based polychemotherapy cannot be judged because of the small number of cases; but the side effects at these patients were registered thoroughly. Side effects of totally 514 therapeutic cycles (460 mg CDDP per patient, 78 mg CDDP per cycle) are presented.

Aged↗

Survival following the documentation of platinum and taxane resistance in ovarian cancer: a single institution experience involving multiple phase 2 clinical trials.

OBJECTIVES: There are very limited data in the oncology literature regarding the survival of women with both platinum and taxane-refractory ovarian cancer. METHODS: To examine this issue, we retrospectively reviewed the survival of patients treated on one (or more) of four previously reported nonrandomized single-agent phase 2 trials (topotecan, liposomal doxorubicin, gemcitabine, docetaxel), involving women with well-characterized platinum/taxane-resistant ovarian, fallopian tube, and primary peritoneal cancers. Following their most recent treatment with both classes of agents, patients must have either not responded to therapy or experienced a treatment-free interval of <3 months before documented disease progression. RESULTS: The median survival of the 111 patients (median age 61) included in this analysis was 6 months (range 1-37 months). Whereas 36 patients (32%) survived for <4 months, 30 patients (27%) lived for > or =12 months following documentation of resistance to both platinum and taxane therapy. CONCLUSION: With currently available antineoplastic drug therapy of platinum/taxane-resistant ovarian cancer, overall survival is relatively short, but a substantial minority of patients can be anticipated to live for periods in excess of 1 year. It remains uncertain whether such unexpectedly prolonged survival results from a biological response to chemotherapy or simply reflects the natural history of disease in a subset of patients with this malignancy.

Adult↗

Non-primary cervical adenocarcinomas.

We reviewed 16 non-primary cervical adenocarcinomas collected during a six year period. Ten tumors originated in the endometrium, three in the ovary and one each in the bladder, colon and fallopian tube. Tumor spread was identified by combined lymphovascular involvement and stromal invasion in five of the 16 cervices, lymphovascular involvement alone in four cervices, stromal invasion alone in two cervices, lymphovascular involvement with stromal invasion and cervical implantation in two cervices and cervical implantation alone in three cervices. The three tumors with surface implantation alone were of endometrial origin, had minimal if any myometrial invasion, no extrauterine metastases and two had malignant peritoneal washings. Of the 13 tumors with cervical lymphovascular involvement and/or stromal metastases, 11 had ovarian, nodal and/or peritoneal metastases. We conclude that cervical implantation occurs exclusively with endometrial adenocarcinomas, that it follows previous cervical instrumentation and that the prognosis is dependent on the histoprognostic features of the primary endometrial tumor. In contrast, cervical lymphovascular involvement and/or stromal metastases usually reflects disseminated pelvic or abdominal malignancy with a poor prognosis. However histological examination may not afford separation of these two lesions if local cervical invasion is advanced, if spread has occurred by more than one mode or if insufficient clinical/surgical information is provided.

Adenocarcinoma↗

A phase II trial of three sequential doublets for the treatment of advanced müllerian malignancies.

OBJECTIVES: In an effort to improve the results of primary chemotherapy for müllerian malignancies a novel chemotherapy program was piloted that delivered three sequential chemotherapy doublets. The primary endpoints were surgically defined response rates and evaluation of toxicity. METHODS: After primary cytoreductive surgery patients were treated with three sequential doublets including three initial cycles of carboplatin and paclitaxel (doublet 1) and then two cycles of cisplatin (day 1) and gemcitabine (days 1 and 8; doublet 2), and finally two cycles of doxorubicin (day 1) and topotecan (days 3,4, and 5; doublet 3). Cycles 4 through 7 were given with G-CSF (Neupogen) support at a dose of 5 mcg/kg/day. After therapy, all women were clinically staged and evaluated by second-look laparoscopy/laparotomy (SLO) if clinical staging was negative for residual disease. RESULTS: A total of 49 eligible patients were enrolled with a median age of 52 (SD 9). Forty-four women had either ovarian cancer or primary peritoneal carcinoma with 3 women diagnosed with fallopian tube carcinoma and 2 with papillary serous carcinoma of the uterus. Eighty-four percent of patients had stage IIIc/IV tumors, with 29% having >1 cm residual disease after primary cytoreductive surgery. Thirty-nine of 49 (80%) patients completed therapy. A total of 283 cycles of chemotherapy were delivered with acceptable toxicities. There were no toxic deaths. Five women were withdrawn from trial (3 for Taxol hypersensitivity, 1 for gemcitabine pulmonary hypersensitivity, and 1 for serious line infection). Neutropenia, typically without fever, was relatively frequent in the first doublet. Nausea and thrombocytopenia were the predominant toxicities in doublet 2. Thirty-nine women completed all cycles of treatment. Thirty-six women had restaging results consistent with a clinical complete response (CR) and underwent SLO. The pathologic CR rate of the patients undergoing SLO was 38%. CONCLUSIONS: Treatment with this sequential doublet regimen is feasible with a 38% pathologic CR rate.

Antineoplastic Combined Chemotherapy Protocols↗

Third-line chemotherapy in platinum- and paclitaxel-resistant ovarian, fallopian tube, and primary peritoneal carcinoma patients.

Ovarian carcinoma is a malignant disease with a high rate of recurrence, necessitating repeated chemotherapy treatments. We conducted a retrospective study in patients with platinum- and paclitaxel-resistant ovarian, fallopian tubes and primary peritoneal carcinoma patients treated at M.D. Anderson Cancer Center. We evaluated the responses, progression-free intervals, and overall survival duration of 51 patients after third-line chemotherapy treatment. The overall response rate was 16% (eight cases) with 2% complete response rate (one case) and 14% partial response rate (seven cases). Stable disease was achieved in 31% (16 cases). The progression-free intervals of 24 patients who had response and stable disease was 7.4 months (range, 1.4-18.4 months). The median overall survival of all patients was 15.8 months (95% CI, 8.1-23.4 months). The median survival duration of eight responders was not significantly different from that of 43 nonresponders, 18.9 months (95% CI, 2.4-35.4 months) versus 15.8 months (95% CI, 6.4-25.2 months), respectively (P = 0.73). In conclusion, third-line chemotherapy in our study results in a modest response and prolongation of progression-free interval without obvious impact on survival. The decision to utilize third-line chemotherapy will be a balance of the limited efficacy, toxicity of the agents, and the expertise of the clinician.

Aged↗

The role of the HER-2/neu oncogene in gynecologic cancers.

OBJECTIVE: The HER-2/neu proto-oncogene (also known as c-erbB2, neu, and HER2) encodes a 185-kDa transmembrane glycoprotein with intrinsic tyrosine kinase activity that resembles the receptor for epidermal growth factor. Aberrant HER-2/neu protein overexpression occurs in human gynecologic adenocarcinomas, including those of the ovary, endometrium, breast, fallopian tube, and cervix, and is secondary to gene amplification and/or overexpression of the p185HER2 protein. METHODS: A Medline literature search revealed numerous studies on HER-2/neu and tumor biology, cancer prognosis, and therapeutic targeting. We present a review of the literature pertinent to gynecologic malignancies. RESULTS: Overexpression of HER-2/neu was found to be a poor prognostic factor for survival from advanced-stage ovarian cancer, node-positive breast cancer, and endometrial cancer. Although a specific ligand has not been definitively identified, HER-2/neu may have unusually complex activation pathways because it can form both homodimeric and heterodimeric associations with other related receptor proteins. Preliminary findings suggest that serum HER-2/neu levels may be used as a tumor marker in a subset of patients with tumors that overexpress the HER-2/neu receptor. Receptor-targeted therapeutics currently being studied include the use of receptor antibodies, liposomally delivered antisense DNA, antigen-activated cytotoxic lymphocytes, and adenovirus-mediated E1A delivery to overexpressing tumor cells. CONCLUSION: HER-2/neu appears to play an important role in the biologic behavior of ovarian, endometrial, and breast cancers and holds potential as a target for oncogene-directed therapies.

Biomarkers, Tumor↗

Phase 2 trial of single agent docetaxel in platinum and paclitaxel-refractory ovarian cancer, fallopian tube cancer, and primary carcinoma of the peritoneum.

OBJECTIVE: Previously reported data have suggested the lack of complete cross-resistance between docetaxel and paclitaxel in ovarian cancer. We wished to evaluate the biological and clinical activity of docetaxel in a patient population with well-characterized platinum and paclitaxel-refractory ovarian cancer. METHODS: In this single-institution phase 2 trial, 30 women with advanced ovarian cancer whose disease had either failed to respond to primary platinum-paclitaxel chemotherapy or where the cancer had progressed within 3 months of their last treatment with both a platinum agent and paclitaxel were treated with single agent docetaxel (75 mg/m(2) q 3 weeks). Due to a prior history of excessive chemotherapy-induced neutropenia, 3 patients initiated treatment at a dose of 60 mg/m(2). RESULTS: The median number of courses of docetaxel delivered on this protocol was 3 (range 1-7), with 7 patients requiring dose reductions due to treatment-related side effects. The most common toxicities included grade 4 neutropenia, neutropenic fever, and grade >/=2 fatigue experienced by 9 (30%), 2 (7%), 5 (17%) patients, respectively. Three patients (10%) achieved both an objective response (by CA-125 criteria) and symptomatic improvement (e.g., decrease in pain and ascites). The durations of responses were 3, 4, and 6 months. CONCLUSION: Single-agent docetaxel has modest, but definite activity in patients with well-characterized platinum and paclitaxel-resistant ovarian cancer. Use of this drug should be considered a rational management approach in appropriately selected patients in this clinical setting.

Adult↗

Phase 2 trial of prolonged administration of oral topotecan in platinum/taxane-refractory ovarian, fallopian tube, and primary peritoneal cancers.

OBJECTIVES: Preclinical and clinical data have demonstrated the importance of schedule in optimizing the cytotoxic potential of topotecan, one of the most active agents in ovarian cancer. The availability of oral topotecan permits the exploration of the clinical utility of prolonged treatment programs employing this drug. METHODS: Patients with platinum/taxane resistant ovarian and primary peritoneal cancers were treated with oral topotecan at an initial fixed dose of 1.5 mg/day for 5 days, followed by a 2-day break, with treatment continued on this schedule until disease progression or unacceptable toxicities. RESULTS: Seven patients (median age 61) were entered into this phase 2 trial before further enrollment was discontinued due to the development of excessive side effects (grade 3: fatigue (n = 3); emesis (n = 1), thrombocytopenia with bleeding (n = 1). Two additional patients noted grade 2 fatigue. Four patients experienced reductions in hemoglobin concentrations >4.0 g/dl from baseline during treatment, with two patients requiring red cell transfusions and two receiving recombinant erythropoietin. Three patients developed grade 3 neutropenia, while there were no episodes of > or =grade 2 diarrhea. Three patients exhibited biological evidence of an anti-neoplastic effect of therapy (>50% declines in serum CA-125 levels). CONCLUSION: Despite the strong theoretical appeal (as well as limited biological evidence of activity in platinum/taxane-refractory disease) associated with prolonging exposure of cycling ovarian cancer cells to topotecan, the specific oral regimen employed in this trial was associated with excessive bone marrow suppression, especially treatment-induced anemia, resulting in an unacceptable incidence of severe fatigue.

Aged↗

Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer.

OBJECTIVE: There is a need to find agents with activity in platinum and taxane refractory ovarian cancer to be employed as second-line therapy in the malignancy. Limited clinical trial experience has suggested that gemcitabine possesses activity in this clinical setting. We wished to further define the level of activity of gemcitabine in women with well-characterized platinum/taxane refractory disease. METHODS: Patients with ovarian or fallopian tube cancer or primary carcinoma of the peritoneum, whose disease had either failed to respond to a platinum and taxane treatment, or had responded but the "treatment free interval (TFI)" was < or =3 months, or if the TFI was >3 months and they had been retreated with the agents and not responded (or experienced a TFI of <3 months), were eligible for treatment on this phase 2 single institution protocol. Gemcitabine was administered weekly (as a 1-h infusion) for 3 weeks, followed by 1-week break. RESULTS: A total of 51 patients were treated on this trial. The initial dose level (1250 mg/m(2)/week) resulted in excessive toxicity (fatigue, fever/chills, bone marrow suppression). The modified starting dose (1000 mg/m(2)/week) resulted in a more acceptable side effect profile. Eight patients (16%) with measurable disease (n = 4) or evaluable disease by CA-125 criteria (n = 4) achieved an objective response (median duration of response: 4 months; range 2-13 months). CONCLUSION: Single agent gemcitabine possesses modest, but definite, activity in patients with well-characterized platinum/taxane resistant ovarian cancer. It is reasonable to consider this drug for second-line (or later) treatment in this clinical setting.

Adult↗

A phase II trial of weekly docetaxel in patients with platinum-resistant epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer.

OBJECTIVE: To determine the activity and tolerability of weekly docetaxel in patients with platinum-resistant mullerian origin tumors. METHODS: Patients with persistent disease, or those recurring less than 6 months after receiving platinum-containing therapy, were eligible for this phase II study. Docetaxel was initially administered at a dose of 40 mg/m(2) on days 1, 8, and 15, with a cycle length of 28 days. This starting dose was subsequently reduced to 30 mg/m(2) due to toxicity. Dexamethasone prophylaxis was administered at a dose of 4 mg PO every 12 hours for 3 doses, starting 12 hours before each dose of docetaxel. RESULTS: Thirty-two patients were enrolled, with a median age of 59 years. The majority of patients received a median of 3 prior regimens, with 45% of the study group having received 4 or more prior regimens. The overall response rate in 29 evaluable patients was 6.9%, with no complete responses. Seventeen percent of patients experienced stable disease. Dose reduction or delay was required in 10 of the first 22 patients enrolled, prompting a reduction in the starting dose to 30 mg/m(2). Hematologic toxicity was generally tolerable, and no patient experienced febrile neutropenia. Non-hematologic toxicity was generally grade 1 in nature, although a combination of multiple low grade toxicities occurring in an individual patient oftentimes mandated dose reduction. CONCLUSIONS: Weekly docetaxel demonstrated modest activity in a heavily pre-treated, platinum-resistant population. A starting docetaxel dose of 30 mg/m(2) would be reasonable for future studies exploring the utility of weekly dosing in less heavily pre-treated patients.

Aged↗