Gynecologic Oncology Fallopian Tube Carcinoma: A Review Dimitrios Pectasides, Eirini Pectasides, Theofanis Economopoulos
Key Words. Primary fallopian tube carcinoma • Diagnosis • Staging • Prognosis • Treatment
Abstract Purpose. Primary fallopian tube carcinoma (PFTC) is a rare tumor that histologically and clinically resembles epithelial ovarian cancer (EOC). The purpose of this study is to review the current available literature data on PFTC. Patients and Results. Early clinical manifestation and prompt investigation often lead to diagnosis at an early stage of disease. However, the diagnosis of PFTC is rarely considered preoperatively and is usually first appreciated by the pathologist. Surgical staging/management and the use of chemotherapy follow
the concepts used in epithelial ovarian cancer (EOC). In contrast to EOC is the importance of early lymphatic spread in this disease. The earlier diagnosis of PFTC leads to an apparent better survival compared with EOC. However, as with EOC, stage and residual tumor are the most important prognostic variables. Conclusion. Until more extensive clinical research has been performed, ovarian carcinoma management principles should be used in clinical practice. The Oncologist 2006;11:902–912
Introduction
[11, 12]. A study from Finland reported that the incidence of PFTC is increasing, with an age-adjusted incidence of 1.2 per million for 1953–1957 to 5.4 per million for 1993–1997 [7]. About 1,200 cases of PFTC have been reported in the literature until now [13, 14].
Primary fallopian tube carcinoma (PFTC) is an uncommon tumor accounting for approximately 0.14%–1.8% of female genital malignancies [1–7]. It is estimated, based on the data obtained from nine population-based cancer registries in the U.S., that the average annual incidence of PFTC is 3.6 per million women per year [8]. In England and Wales, 40 cases of PFTC and 4,500 cases of epithelial ovarian cancer (EOC) are registered annually [9]. Furthermore, data from an ovarian cancer screening study that followed up a cohort of 22,000 postmenopausal women revealed a higher than expected ratio of PFTC to EOC among these volunteers [10]. It is also possible that the true incidence of PFTC has been underestimated [9] because PFTC may have been mistakenly identified as ovarian tumors during initial surgery and/or during microscopic examination by a pathologist, as the histological appearance of these tumors are identical
Etiology The etiology of this cancer is unknown. Hormonal, reproductive, and possibly genetic factors thought to increase EOC risk might also increase PFTC risk. High parity has been reported to be protective [7], and a history of pregnancy and the use of oral contraceptives decreases the PFTC risk significantly [15]. It has been reported that there is no statistically significant correlation between PFTC and age, race, weight, education level, pelvic inflammatory disease, infertility, previous hysterectomy, endometriosis, lactose intolerance, or smoking [11, 15, 16]. Meng et al. [17] found
Correspondence: D. Pectasides, M.D., Second Department of Internal Medicine, Propaedeutic, Oncology Section, Attikon University Hospital, Rimini 1, Haidari, Athens, Greece. Telephone: 210-5831691, 210-6008610; Fax: 210-5831690, 210-6008610; e-mail:
[email protected] Received March 11, 2006; accepted June 22, 2006. ©AlphaMed Press 1083-7159/2006/$20.00/0 doi: 10.1634/ theoncologist.11-8-902
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Second Department of Internal Medicine, Propaedeutic, Oncology Section, University of Athens, Attikon University Hospital, Haidari, Athens, Greece
Pectasides, Pectasides, Economopoulos
Clinical Manifestations PFTC most frequently occurs between the fourth and sixth decades of life [29, 30], with a median age of occurrence of 55 years (range, 17–88 years). However, PFTC has been reported in young girls aged 17–19 [31–34]. Patients with PFTC appear to have a shorter history of symptoms than those with EOC [35]. The clinical symptoms and signs of PFTC are shown in Table 1 [11, 30, 36 –41]. These symptoms are not specific. Latzko’s triad of symptoms, consisting of intermittent profuse serosanguinous vaginal discharge, colicky pain relieved by discharge, and abdominal or pelvic mass has been reported in 15% of cases [34]. Hydrops tubae profluens, a pathognomonic feature, implies intermittent discharge of clear or blood-tinged fluid spontaneously or on pressure followed by shrinkage of an adnexal mass and occurs in 5% of patients. PFTC is rarely asymptomatic, in contrast to EOC. In many cases, the preoperative diagnosis of PFTC is extremely rare [26, 29, 42, 43]. The rate of preoperative diagnosis was in the range of 0%–10% [6, 44, 45]. Vaughan et al. [46] reported a rate of 21% of preoperative diagnosis, Baekelandt et al. [28] reported a rate of only 2%, and Meng et al. [17] reported that an intraoperative diagnosis is missed in up to 50% of patients. Some patients have been found to have extensive pelvic tumor, perhaps manifested by a tubo-ovarian mass. Even when such disease is resected, it is often impossible on histopathologic examination to determine the origin of the tumor. These cases are almost always classified as ovarian in origin because ovarian cancer is more common than PFTC [9]. When compared with EOC, PFTC is often diagnosed at an earlier stage because of abdominal pain secondary to tubal distention [47–50]. However, a diagnosis of PFTC may be suspected in cases of postmenopausal
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bleeding or spotting with negative diagnostic curettage. Pap smear positivity occurs in 10%–36% of cases [34]. The Pap smear shows abnormal, suspicious, or poorly differentiated cells or glands alternating with negative smear [34]. Also, psammoma bodies found in the Pap smear are suggestive of gynecologic malignancy, and more detailed examination is required [51].
Imaging Imaging routinely carried out for suspected gynecologic malignancies includes ultrasound, computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen. Of course, imaging techniques do not safely rule out the presence of malignancy or conversely rule in that possibility, and their findings cannot change the management of PFTC. Transvaginal and transabdominal ultrasound is an essential imaging technique in the diagnostic workup of patients with possible tubal pathology [52, 53]. Timor-Tritsch and Rottem [54] demonstrated the benefits of transvaginal over transabdominal ultrasound in the imaging of fallopian tubes. The echographic appearance of fallopian tubes is nonspecific, mimicking other pelvic diseases, such as tubo-ovarian abscess, ovarian tumor, and ectopic pregnancy. Echogram shows a cystic mass with spaces and mural nodules, a sausage-shaped mass, or a multilobular mass with a cog-and-wheel appearance [55–57]. Low-impedance vascular flow within the solid components has been reported [58]. In addition, it was demonstrated that transvaginal ultrasound examination with color Doppler can detect areas of neovascularization within the fallopian tube and thus may aid in the preoperative diagnosis of PFTC. Three-dimensional Doppler can show tubal wall irregularities such as papillary protrusions and pseudosepta and depictions of vascular abnormalities (arteriovenous shunts, microaneurysms, tumor lakes, blind ends, and dichotomous branching typical of malignant tumor vessels) [59]. The lesion can have the appearance of a small, solid, lobulated mass on CT scan or on MRI. On CT scan, the lesion has an attenuation equal to that of other soft tissue masses and enhances less than the myometrium. On T1weighted MR images, the tumor is usually hypointense; on T2-weighted MR images the tumor is often homogeneously hyperintense. Imaging can most often detect solid and cystic components with papillary projections, which on MRI can be remarkably enhanced by the administration of gadolinium [60]. Associated findings include peritumoral ascites, intrauterine fluid collection, and hydrosalpinx [61]. MRI seems to be better than CT scan or ultrasound in detecting tumor infiltration of the bladder, vagina, pelvic sidewalls, pelvic fat, and rectum.
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a fivefold higher bilateral occurrence in infertile patients than in fertile patients, and Hanton et al. [18] reported a better prognosis in nulliparous women. PFTC has been described in high-risk breast–ovarian cancer families with germ-line BRCA-1 and BRCA-2 mutations [19–22]. Some studies suggested that the frequency and structure of the chromosomal changes (BRCA-1 or BRCA-2 mutations) observed in PFTC had similarities with those found in breast, serous ovarian, and uterine carcinomas, and consequently, a common molecular pathogenesis was claimed [22–26]. Some cases of occult PFTC have been detected at prophylactic salpingo-oophorectomy in BRCA1 mutation carriers [27]. Therefore, the risk for this malignancy should be considered when prophylactic surgery is performed in such high-risk women [28]. In the case of prophylactic surgery, the uterus and the intrauterine portion of the fallopian tube should be removed.
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Table 1. Clinical features of primary fallopian tube carcinoma Clinical Features Vaginal bleeding or spotting Abdominal pain, colicky or dull Abdominal or pelvic mass Ascites Rare presentations (acute abdomen, palpable inguinal node, umbilical-bone cerebral metastases, cerebellar degeneration) [38–41] Postmenopausal bleeding or spotting with negative Pap smear
CA-125 Level
the tube and arises from the endosalpinx; (b) Histologically, the pattern reproduces the epithelium of the mucosa and often shows a papillary pattern; (c) If the wall is involved, the transition between benign and malignant epithelium should be demonstrable; and (d) The ovaries and endometrium are either normal or contain less tumor than the tube. Molecular biology studies have shown that PFTC is characterized by an extremely unstable phenotype with highly scattered DNA ploidy patterns and frequent p53 gene alterations [75–79].
Pattern of Spread and Staging Tubal carcinoma spreads in much the same manner as EOC, principally by the transcelomic exfoliation of cells that implant throughout the peritoneal cavity. In approximately 80% of patients with advanced disease, metastases are confined to the peritoneal cavity [41]. Tumor spread can also occur by means of contiguous invasion, transluminal migration, and hematogenous dissemination [80]. Bilateral tubal involvement has been reported in 10%–27% of cases [10, 47, 48, 67, 71, 81]. Gadducci et al.
Cytology Several authors state that the cervicovaginal smear is an inadequate diagnostic tool and no one would consider using it for the diagnosis of PFTC. Positive Pap smears have been reported in only 0%–23% of cases [6, 51, 67–70]. The discrepancy between an abnormal Pap smear and negative findings on colposcopy, cervical biopsy, and endometrial curettage should be considered suspicious for PFTC.
Pathology The diagnosis of PFTC is usually first made by a pathologist on histopathological examination. The most common histological types are shown in Table 2 [50, 71–75]. Serous tumors are graded with respect to their differentiation and extent of solid components: most tumors are poorly differentiated [48, 50, 71] (Table 3). Because it is difficult to differentiate PFTC from EOC, patients with at least one of the following criteria should have the diagnosis of PFTC [72]: (a) The main tumor is in
Table 2. Frequency of different histologic subtypes in primary fallopian tube carcinoma (PFTC) and epithelial ovarian cancer (EOC) Serous Endometrioid Mixed Undifferentiated Clear cell Transitional Mucinous
PFTC 49.5%–83.3% 8.3%–50% 3.9%–16.7% 7.8%–11.3% 1.9% 11.7% 3%–7.6%
EOC 75% (60%–80%) 20% (15%–24%) 3% 1%–2% 5% (3.7%–12.1%) 1%–2% 2.4%–19.9%
Table 3. Grading in primary fallopian tube carcinoma (PFTC) and epithelial ovarian cancer (EOC) Grade 1 Grade 2 Grade 3
PFTC 15%–20% 20%–30% 50%–65%
EOC 20% 30% 50%
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CA-125 is a useful tumor marker for the diagnosis, assessment of response to treatment, and detection of tumor recurrence during follow-up. The CA-125 antigen is often expressed by PFTC [62]. Although CA-125 per se is not diagnostic for PFTC, >80% of patients have elevated pretreatment serum CA-125 levels [34, 49]. Elevated serum CA125 levels have been detected more frequently in advanced or recurrent disease [10, 49, 62–64]. Gadducci et al. [48] reported that preoperative serum CA-125 levels were >35 U/ ml in 85.3% of cases (68.7% for stage I–II and 94.7% for stage III–IV). The pretreatment serum CA-125 level is an independent prognostic factor of disease-free survival and overall survival (OS) in patients with PFTC [10, 34]. Serum CA-125 levels postsurgery have also been associated with response to chemotherapy [19, 64, 65]. CA-125 is also a useful marker for post-treatment follow-up. It is an early and sensitive marker for tumor progression during follow-up [63–66]. It has been reported that the lead time (elevated serum CA-125 levels prior to clinical or radiological diagnosis of recurrence) is 3 months (range, 0.5–7 months) [34].
Percentage 50%–60% 30%–49% 60% (range, 12%–84%) 15%
Pectasides, Pectasides, Economopoulos
Treatment Surgery Surgery is the treatment of choice for PFTC. Surgical principles are the same as those used for ovarian cancer. The majority of patients in the literature had clearly suboptimal staging by today’s standards [46]. Aggressive cytoreductive surgery with removal of as much tumor as possible is warranted in patients with advanced disease. If it is impossible
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to achieve optimal debulking despite maximum effort, surgery should be attempted again after a few courses of chemotherapy. Very aggressive forms of surgery should only be considered in highly individualized patients [88]. Considering the strong tendency for lymphatic spread of the tumor, a systematic pelvic and para-aortic lymphadenectomy is preferred to lymph node sampling [48, 89, 90]. Klein et al. [89] reported that the median survival times were 43 and 21 months, respectively, in patients with and without lymph node dissection. In advanced disease, the bulk of extratubal disease and postoperative residual disease >2 cm are adverse prognostic factors [13, 46]. In young patients who want to retain fertility, limited surgery can be considered for patients with an in situ carcinoma and in those women with stage I and grade I carcinoma [34].
Second-Look Laparotomy As in the case of EOC, second-look laparotomy does not have a role in the management of PFTC [91]. In EOC, second-look laparotomy has not been proven to be beneficial since 50% of patients with a surgical complete response still go on to relapse. In addition, there is no curative second-line therapy for those patients with positive findings at secondlook laparotomy. A review of 310 patients included in 13 literature series revealed that 32 (62.7%) of the 51 patients submitted to second-look operation were found to be in pathologic complete remission (pCR) [92]. Recurrence was recorded for 22% of these 32 patients. A negative secondlook laparotomy is associated with longer survival. Secondlook laparotomy should currently be reserved for patients enrolled in clinical trials.
Radiotherapy Radiotherapy could possibly be considered either as adjuvant therapy for early-stage patients [2, 5, 28, 45, 46, 73, 85, 93–96], for stage III residual negative patients, or in the relapse setting. Although radiotherapy has been used traditionally in the past as an adjuvant therapy for PFTC, its role in the era of effective chemotherapy is less well defined and controversial. In view of its low efficacy and high rate of serious complications, the use of postoperative radiotherapy in the treatment of patients with PFTC is no longer recommended. Intraperitoneal instillation of radioisotopes did not seem to reduce the recurrence risk in early-stage disease [12, 47].
Adjuvant Chemotherapy Based on the propensity for microscopic distant spread and the relatively high risk for recurrence despite complete surgical resection, chemotherapy seems to have a strong rationale as adjuvant treatment for patients with early-stage disease;
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[48] reported that both tubes were involved in 31.8% of 88 cases (23.8% of stage I–II cases and 39.1% of stage III–IV cases) and Schiller and Silverberg [81] reported bilateral involvement in 9.1% of 11 cases (5.3% of stage I–II cases and 30.4% of stage III–IV cases). Penetration of the serosa is an ominous sign associated with a poor prognosis [44, 50, 80, 81]. In the latter stages of the disease, the natural course is more parallel to that of EOC. Data from the literature indicate that patients with PFTC have a higher rate of retroperitoneal and distant metastases than those with EOC [12, 48–50, 70, 80, 82–84]. Metastases to the para-aortic lymph nodes have been documented in 33% of the patients with all stages of disease [85]. The PFTC is richly permeated with lymphatic channels that drain into the para-aortic lymph nodes through infundibulopelvic lymphatics. An intrapelvic course with drainage into the superior gluteal lymph nodes is also possible. The existence of anastomoses with lymphatics of the uterus in the round ligament may explain the development of inguinal node metastases [85]. Semrad et al. [2] reported that a large number of patients with an unknown nodal status at the initial staging who later developed recurrence probably had persistent disease in their lymphatics. On routine lymphadenectomy, 42%–59% of patients show lymph node metastases, with almost equal involvement of the para-aortic and pelvic lymph nodes [34]. Compared with EOC, nodal spread is more common in PFTC, and therefore these observations provide the basis for recommending lymph node sampling as a mandatory procedure of surgical staging [28, 48]. Surgical understaging, as in the case of EOC, was common in older series. Therefore, many of the stage I–II patients were probably understaged because of the lack of surgical retroperitoneal assessment. The staging of PFTC is based on the surgical findings at laparotomy. The International Federation of Gynecology and Obstetrics (FIGO) EOC staging system has been adapted to apply to PFTC (Table 4) [19, 86, 87]. PFTC is often diagnosed at an earlier stage than EOC. In general, 20%–25% of patients have stage I, 20% have stage II, 45%– 50% have stage III, and 5%–10% have stage IV [34].
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Table 4. Staging of primary fallopian tube carcinoma (PFTC) FIGO TNM Primary tumor cannot be assessed Tx No evidence of primary tumor TO Carcinoma in situ (pre-invasive carcinoma) Tis I Carcinoma confined to fallopian tubes T1 IA Tumor confined to 1 tube without infiltrating the serosal surface: no ascites T1a IB Tumor confined to both tubes without infiltrating the serosal surface: no ascites T1b IC Tumor confined to 1 or both tubes with extension onto/through the tubal serosa or with positive T1c malignant cells in the ascites or positive peritoneal washings II Tumor involving both tubes with pelvic extension T2 IIA Extension and/or metastases to uterus and/or ovaries T2a IIB Extension to other pelvic organs T2b IIC Stage IIA or IIB with positive malignant cells in the ascites or positive peritoneal washings T2c III Tumor involving 1 or both tubes with peritoneal implants outside the pelvis and/or positive regional T3 and/or N1 lymph nodes IIIA Microscopic peritoneal metastases outside the pelvis T3a IIIB Macroscopic peritoneal metastases outside the pelvis ≤2 cm in greatest dimension T3b and/or N1 IIIC Peritoneal metastases more than >2 cm in greatest dimension and/or positive regional lymph nodes T3c and/or N1 IV Distant metastases beyond the peritoneal cavity. Positive pleural cytology and/or parenchymal liver M1 metastases Abbreviations: FIGO, International Federation of Gynecology and Obstetrics; TNM, Tumor–Nodes–Metastasis. 0
therapy arm and 74% in the observation arm (difference, 8%; hazard ratio [HR], 0.67; p = .008). The recurrence-free survival rate at 5 years was also better in the adjuvant chemotherapy arm than in the observation arm (76% vs. 65%; difference, 11%; HR, 0.64; p = .001). The same treatment strategy for early-stage disease could also be of benefit for patients with early-stage, high-risk PFTC.
Combination Chemotherapy for Advanced Disease The current gold standard chemotherapy for EOC in North America is a platinum–taxane combination, and in Britain, it is platinum followed on relapse by a taxane. There are very few data that are extractable from the literature with regard to PFTC. Several authors using cisplatin-based chemotherapy in patients with advanced PFTC reported overall responses rates of 53%–92% [4, 49, 50, 68, 70, 92, 94, 96, 99]. Peters et al. [50] reported a 75% complete response rate in a study of 46 patients with advanced or recurrent PFTC. Similarly, Gadducci et al. [48], among the 45 patients with advanced disease treated with cisplatin-based chemotherapy, reported complete and partial responses in 64.4% and 17.8% of patients, respectively. The 5-year survival rate was 56% for the complete responders, whereas all the partial responders died within 56 months and all patients with stable or progressive disease died within 21 months. Literature data
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however, very few data for this malignancy are currently available in the literature [6, 12, 47, 50, 67, 70, 97]. Singleagent chemotherapy does not seem to be effective, while platinum-based combination chemotherapy is the most commonly used adjuvant therapy for these patients, identical to EOC patients [41, 44, 68, 98]. Patients with stage IA and IB may not require adjuvant therapy, as for patients with EOC. All other patients are treated with platinum-based combinations. In addition, early-stage patients with tumors infiltrating the serosa or with pre- or intra-operatively ruptured tumors should receive chemotherapy. Peters et al. [50] reported no statistically significant difference in survival with the addition of single-agent chemotherapy in patients with disease limited to the tubes. Similarly, Gadducci et al. [48] reported no significant difference in the recurrence rate between patients with stage I disease who were treated with platinum-based combination chemotherapy and those who were not. However, the International Collaborative Ovarian Neoplasm (ICON)-1 and Adjuvant ChemoTherapy In Ovarian Neoplasm (ACTION) studies have shown that chemotherapy for early-stage patients with ovarian cancer did confer a survival benefit [98]. Nine hundred twenty-five patients (477 in ICON-1 and 448 in ACTION) who had surgery for early-stage ovarian cancer were randomly assigned to receive either platinum-based adjuvant chemotherapy (n = 465) or observation (n = 460) until chemotherapy was indicated. The OS rates at 5 years were 82% in the chemo-
Pectasides, Pectasides, Economopoulos
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possibly be recommended for the management of optimally debulked PFTC. Another taxane, docetaxel, at a dose of 75–100 mg/m 2, was administered in 30 assessable for response patients with EOC, PFTC, and peritoneal carcinomatosis who failed paclitaxel-based chemotherapy [103]. The overall response rate was 23% (one complete response and six partial responses), with a median survival time of 44 weeks (9.5 months). Nine patients had stable disease, and 14 had disease progression. Among the 19 patients who progressed during prior paclitaxel treatment, two (11%) responded to docetaxel, compared with five (45%) of the 11 patients in other paclitaxel-resistance categories. Recently, the combination of carboplatin (AUC 6) and docetaxel (60 mg/m2) delivered every 3 weeks for six courses showed activity (objective responses for 32 of 42 [81%] assessable patients) in the treatment of patients with EOC, PFTC, and peritoneal carcinomatosis who had either received no prior chemotherapy or had experienced a treatment-free interval of >2 years before developing disease recurrence [108]. The major toxicity was bone marrow suppression. The same treatment strategy should be followed in the case of second-line chemotherapy for recurrent PFTC. Platinum-sensitive patients (relapse after 6 months) should be retreated with a platinum with or without paclitaxel, while platinum-refractory (progression during platinum-based therapy) or platinum-resistant (relapse within 6 months) patients should be treated with nonplatinum agents such as topotecan or liposomal doxorubicin. However, response rates of platinum analogues in the “less than 6 months group” are still in the 10%–15% range, and therefore one could argue that in all but truly platinum-refractory disease there is a role for using platinum analogues, given that the other agents in this scenario have similar low response rates. Topotecan has been investigated as salvage chemotherapy in patients who failed platinum- and paclitaxelbased chemotherapy [109, 110]. Dunton and Neufeld [111] used topotecan to treat a patient with PFTC who failed carboplatin and paclitaxel chemotherapy. That patient demonstrated a complete clinical response to topotecan. Because myelosuppression is the dose-limiting toxicity (DLT) of topotecan when given at a dose of 1.5 mg/m2 for 5 days, new schedules of topotecan administration are currently being investigated for recurrent EOC, PFTC, and peritoneal carcinomatosis [112, 113]. Brown et al. [112] conducted a trial to determine the DLT and maximum tolerated dose (MTD) of topotecan administered for 3 days every 21 days. Twenty patients with recurrent EOC, PFTC, or peritoneal carcinoma were treated with escalating doses of topotecan beginning at 2.50 mg/m 2 on an outpatient basis. Colonystimulating factors were not employed prophylactically but
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on small series showed the possible value of cyclophosphamide, doxorubicin, and cisplatin (the CAP regimen) and paclitaxel-containing regimens [49, 70, 94, 100, 101]. Pectasides et al. [94] treated 14 patients with a CAP combination (10 patients) or carboplatin plus cyclophosphamide (four patients). Eight of these patients had a complete clinical response, and two had partial responses. Among the eight complete responders, five patients underwent a second-look operation, and pCR was confirmed in four of five of them. Very few data exist on the activity of paclitaxel as firstline chemotherapy in patients with PFTC [100, 102, 103]. Gemignani et al. [104] reported their experience on the use of paclitaxel-based chemotherapy after initial surgery in 24 patients with PFTC, of whom 17 had stage III–IV disease. Twenty-three patients received paclitaxel at a dose of 135–175 mg/m2 with carboplatin or cisplatin; the majority, 17 of 23 (74%), received carboplatin. One patient received paclitaxel alone. The median disease progression-free survival rate at 3 years was 67% in the optimally debulked group, compared with 45% in the suboptimally debulked group. They concluded that optimally cytoreduced patients with PFTC treated with a paclitaxel-based chemotherapy regimen have an excellent possibility of survival. Similarly, Baekelandt et al. [105] administered the combination of carboplatin (area under the concentration–time curve [AUC] 6) plus paclitaxel (175 mg/m2) to eight patients with PFTC, of whom four were chemotherapy-naïve and four had recurred after a platinum-free interval of at least 6 months. Three (37.5%) patients achieved a complete response and four (50%) had a partial response, for an overall response rate of 87.5%. With regard to relapse therapy, all the information comes from EOC. Paclitaxel has been shown to have activity in platinum-pretreated patients with PFTC [104–107]. Tresukosol et al. [106] reported that paclitaxel at a dose of 200 mg/m2 produced a complete response in a patient with recurrent platinum-resistant disease, and Ichikawa et al. [107] reported that the combination of carboplatin (AUC 6) plus paclitaxel (180 mg/m 2) achieved a complete response in a patient with a platinum-pretreated tumor. In EOC, there is evidence that using intraperitoneal therapy as one component may be more effective than i.v. chemotherapy for stage III, residual
