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Primary carcinoma of the fallopian tube--a retrospective analysis of 115 patients. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

Incidence and prognostic factors of primary carcinoma of the Fallopian tube were studied in a retrospective multi-centre analysis of 115 women during the period 1980 to 1990. Data of 28 departments (university as well as general hospitals) were included in the present study which was designed to evaluate the current diagnosis and treatment of carcinoma of the Fallopian tube in Austria, and to compare the results with those from the literature. Stages were classified according to the modified FIGO-system for ovarian cancer; grading followed the criteria of Hu et al. (1950). The mean age of the patients was 62.5 years. Forty-seven (40.9%) tumours were found to be in stage I, 20 (17.4%) in stage II, 34 (29.6%) in stage III, and 14 (12.1%) in stage IV. In 82 patients, the tumour could be completely removed. The surgical method applied in 95 cases was removal of the uterus, the adnexa, and/or the omentum, or lymph nodes. Postoperatively patients underwent adjuvant therapy which was either irradiation (n = 40; 34.8%), or chemotherapy (n = 49; 42.6%); 26 women (22.6%) had no therapy after operation. The 5-year survival rate for all stages was 36.5%. In stages I and II the 5-year survival was 50.8% compared to 13.6% in stages III and IV. FIGO-stage I and II and a residual tumour less than 2 cm in advanced disease had a prognostically favourable impact, which was proven in univariate as well as multivariate analysis.

Adult↗

A comparative analysis of management and prognosis in stage I and II fallopian tube carcinoma and epithelial ovarian cancer.

Staging and surgical as well as post-operative treatment of primary Fallopian tube carcinoma (FTC) followed the lines established for primary ovarian cancer (OC). In a nationwide retrospective analysis we were able to find a distinct difference between these two tumours. A total of 262 patients, 68 with FTC and 194 with OC, in stage I and II were included into this study. A univariate as well as a multivariate analysis for survival was performed, including factors such as age, histological type, grading and surgical and adjuvant treatment. A significantly poorer outcome (P = 0.0002) for FTC patients with a 5-year survival of 50.8% compared with 77.5% for OC patients was observed. This finding was persistent and independent of any investigated factor, in univariate as well as multivariate analyses. Therefore, we feel that a more aggressive therapeutic approach to the treatment of FTC even in early stages can be recommended. On the other hand, the retrospective character of our study has to be taken into account.

Age Factors↗

p53 mutation is associated with high S-phase fraction in primary fallopian tube adenocarcinoma.

Fallopian tube carcinoma (FTC) is a rare but lethal gynaecological malignancy. Four out of seven FTCs were identified with three point missense mutations, one single base deletion and one silent point mutation in the p53 gene. Genital-type HPV sequences were not detected. The S-phase fraction of tumours with mutant and wild-type p53 was 25.74% (median) and 12.55% (median) respectively.

Adenocarcinoma↗

A phase I dose-finding study of a combination of pegylated liposomal doxorubicin (Doxil), carboplatin and paclitaxel in ovarian cancer.

Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease. A dose finding study of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first-line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(-2); doxil 20, 30, 40 and 50 mg m(-2). Schedules examined included treatment cycles of 21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with doxil being administered every other course (q 42). The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(-2) and doxil 30 mg m(-2) q 21. Reducing the paclitaxel dose to 135 mg m(-2) did not allow the doxil dose to be increased. Delivering doxil on alternate cycles at doses of 40 and 50 mg m(-2) also resulted in dose-limiting toxicities. The recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175 mg m(-2), doxil 30 mg m(-2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(-2), doxil 20 mg m(-2) q 21. Grade 3/4 haematologic toxicity was common at the recommended phase II doses but was short lived and not clinically important and non-haematologic toxicities were generally mild and consisted of nausea, paraesthesiae, stomatitis and palmar plantar syndrome.

Adult↗

Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up.

A retrospective study was performed to assess the histopathologic findings in high-risk women undergoing bilateral prophylactic (salpingo)-oophorectomy. The medical files of BRCA1 or BRCA2 mutation carriers and members of a hereditary breast/ovarian cancer (HBOC) family, who had undergone prophylactic surgery, were reviewed. In all, 38 women underwent a bilateral oophorectomy (26 BRCA1, three BRCA2 and nine HBOC, respectively). A total of 90 women underwent bilateral salpingo-oophorectomy (58 BRCA1, six BRCA2, one BRCA1 and 2, 25 HBOC, respectively). At the time of salpingo-oophorectomy, five of 58 BRCA1 carriers (8.6%) were diagnosed with an occult carcinoma: two fallopian tube carcinomas, two ovarian carcinomas and one case was defined as a fallopian tube/ovarian carcinoma. No occult carcinomas were found in the other groups. Of the 38 patients, who underwent a bilateral oophorectomy (mean follow-up 45 months), three of 26 BRCA1 mutation carriers (3.4 in 100 women-years) developed peritoneal papillary serous carcinoma (PPSC) during follow-up. So far, no PPSC have occurred in the 90 women, who underwent a salpingo-oophorectomy (mean follow-up 12 months), including 58 BRCA1 carriers (0 in 60 in women-years). These results contribute to the thesis that BRCA1 germline mutation carriers are not only at risk for ovarian cancer, but also for fallopian tube carcinoma and peritoneal papillary serous carcinoma. Our data suggest that PPSC risk among BRCA2 carriers is lower than among BRCA1 carriers.

Adult↗

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer.

A total of 53 women with chemotherapy-naïve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, +/- decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.

Adult↗

SCOTROC 2A: carboplatin followed by docetaxel or docetaxel-gemcitabine as first-line chemotherapy for ovarian cancer.

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

Adult↗

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel-irinotecan as first-line therapy for ovarian cancer.

The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200 mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55-78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted.

Adult↗

A comparison of national cancer registry and direct follow-up in the ascertainment of ovarian cancer.

The National Health Service Central Register (NHSCR) and direct follow-up were used to document ovarian and fallopian tube cancers in 22000 women from 1986 to 1993. Direct follow-up identified 47/49 cases (96%) and the NHSCR 38/49 (78%). NHSCR ascertainment was incomplete and direct follow-up provided additional information. These findings have implications for interpretation of national cancer statistics and for use of the NHSCR in research trials.

Cohort Studies↗

A phase I/II trial of rAd/p53 (SCH 58500) gene replacement in recurrent ovarian cancer.

PURPOSE: To determine the safety, gene transfer, host immune response, and pharmacokinetics of a replication-deficient adenovirus encoding human, recombinant, wild-type p53 (SCH 58500) delivered into the peritoneal cavity (i.p.) alone and sequentially in combination with platinum-based chemotherapy, of patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer containing aberrant or mutant p53. METHODS: SCH 58500 was administered i.p. to three groups of patients with heavily pretreated recurrent disease. Group 1 (n=17) received a single dose of SCH 58500 escalated from 7.5 x 10(10) to 7.5 x 10(12) particles. Group 2 (n=9) received two or three doses of SCH 58500 given alone for one cycle, and then with chemotherapy for two cycles. The SCH 58500 dose was further escalated to 2.5 x 10(13) particles/dose in group 2. A third group (n=15) received a 5-day regimen of SCH 58500 given at 7.5 x 10(13) particles/dose per day i.p. alone for cycle 1 and then with intravenous carboplatin/paclitaxel chemotherapy for cycles 2 and 3. RESULTS: No dose-limiting toxicity resulted from the delivery of 236/287 (82.2%) planned doses of SCH 58500. Fever, hypotension abdominal complaints, nausea, and vomiting were the most common adverse events. Vector-specific transgene expression in tumor was documented by RT-PCR in cells from both ascitic fluid and tissue biopsies. Despite marked increases in serum adenoviral antibody titers, transgene expression was measurable in 17 of 20 samples obtained after two or three cycles of SCH 58500. Vector was detectable in peritoneal fluid by 24 hours and persisted for as long as 7 days whereas none was detected in urine or stool. There was poor correlation between CT scans and CA125 responses. CA125 responses, defined as a greater than 50% decrement in serum CA125 from baseline, were documented in 8 of 16 women who completed three cycles of the multidose regimen. CONCLUSION: CT scans are not a valid measure of response to i.p. SCH 58500 due to extensive adenoviral-induced inflammatory changes. Intraperitoneal SCH 58500 is safe, well tolerated, and combined with platinum-based chemotherapy can be associated with a significant reduction of serum CA125 in heavily pretreated patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.

Adenoviridae↗

Genome-wide-array-based comparative genomic hybridization reveals genetic homogeneity and frequent copy number increases encompassing CCNE1 in fallopian tube carcinoma.

Fallopian tube carcinoma (FTC) is a rare, poorly studied and aggressive cancer, associated with poor survival. Since tumorigenesis is related to the acquisition of genetic changes, we used genome-wide array comparative genomic hybridization to analyse copy number aberrations occurring in FTC in order to obtain a better understanding of FTC carcinogenesis and to identify prognostic events and targets for therapy. We used arrays of 2464 genomic clones, providing approximately 1.4 Mb resolution across the genome to map genomic DNA copy number aberrations quantitatively from 14 FTC onto the human genome sequence. All tumors showed a high frequency of copy number aberrations with recurrent gains on 3q, 6p, 7q, 8q, 12p, 17q, 19 and 20q, and losses involving chromosomes 4, 5q, 8p, 16q, 17p, 18q and X. Recurrent regions of amplification included 1p34, 8p11-q11, 8q24, 12p, 17p13, 17q12-q21, 19p13, 19q12-q13 and 19q13. Candidate, known oncogenes mapping to these amplicons included CMYC (8q24), CCNE1 (19q12-q21) and AKT2 (19q13), whereas PIK3CA and KRAS, previously suggested to be candidate driver genes for amplification, mapped outside copy number maxima on 3q and 12p, respectively. The FTC were remarkably homogeneous, with some recurrent aberrations occurring in more than 70% of samples, which suggests a stereotyped pattern of tumor evolution.

Carcinoma↗

Ovarian endodermal sinus tumor in a 76-year-old woman.

A 76-year-old woman underwent surgery for pelvic mass, during which a 13 x 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later.

Age Factors↗

Preoperative diagnosis of the primary fallopian tube carcinoma by three-dimensional static and power Doppler sonography.

OBJECTIVE: To investigate whether three-dimensional static and power Doppler ultrasound improves the diagnosis of primary Fallopian tube carcinoma. METHODS: During a 2-year period five cases of primary Fallopian tube carcinoma were selected from a cohort of 520 patients with a previous scan suggestive of an adnexal tumor. RESULTS: Tubal malignancy occurred in patients between 49 and 64 years, with presenting symptoms such as pain, vaginal bleeding and leukorrhea. CA 125 was elevated in three cases of tubal carcinoma with stages II and III, while in two patients with stage I, CA 125 was within the normal limits. Two-dimensional ultrasound demonstrated sausage shaped cystic masses with papillary projections in two patients and a complex adnexal mass in one patient. Three-dimensional ultrasound revealed sausage shaped cystic and/or complex masses with papillary projections in all five cases of tubal malignancy. In one patient preoperative 3-D ultrasound correctly predicted bilateral tumors, while 2-D transvaginal sonography found only unilateral changes. Additional 3-D power Doppler examination depicted vascular geometry typical for malignant tumor vessels such as arteriovenous shunts, microaneurysms, tumoral lakes, blind ends and dichotomous branching in each of the cases with Fallopian tube carcinoma. CONCLUSIONS: Three-dimensional ultrasound allows precise depiction of tubal wall irregularities such as papillary protrusions and pseudosepta. Improved understanding of anatomical relationships may aid in distinguishing ovarian from tubal pathology. Multiple sections of the tubal sausage like structures enable determination of local tumor spread and capsule infiltration. Study of the vascular architecture in cases of Fallopian tube malignancy is further enhanced using 3-D power Doppler imaging.

Aged↗

Primary fallopian tube carcinoma: the Queensland experience.

The purpose of this study was to review the experience with fallopian tube carcinoma in Queensland and to compare it with previously published data. Thirty-six patients with primary fallopian tube carcinoma treated at the Queensland Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective clinicopathologic study. All patients had primary surgery and 31/36 received chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal pain (14/36) were the most common presenting symptoms at the time of diagnosis. Median follow-up was 70.3 months and the median overall survival was 68.1 months. Surgical stage I disease (P = 0.02) and the absence of residual tumor after operation (P = 0.03) were the only factors associated with improved survival. Twenty of the 36 patients (55%) presented with stage I disease and survival was 62.7% at 5 years. No patient with postoperative residual tumor survived. The majority of the patients with fallopian tube carcinoma present with stage I disease at diagnosis, but their survival probability is low compared with that of other early stage gynecological malignancies. If primary surgical debulking cannot achieve macroscopic tumor clearence, the chance of survival is extremely low.

Abdominal Pain↗