子宫内膜浆液性乳头状癌组织中Her-2/neu基因的扩增和蛋白表达及其意义

目的 检测Her-2/neu基因在子宫内膜浆液性乳头状癌(UPSC)中的扩增和蛋白表达情况,并分析其临床意义.方法 回顾性分析1996年1月-2006年1月在复旦大学附属肿瘤医院手术治疗的36例UPSC患者的临床病理资料,分别用显色原位杂交和免疫组化法检测Her-2/neu基因在UPS组织中的扩增和蛋白表达情况,并对两种方法进行对比分析;采用单因素log-rank检验、多因素Cox同归法分析影响UPSC预后的因素.同时随机选择同期收治、临床资料完整的136例Ⅰ型子宫内膜样腺癌作为对照,行免疫组化法检测其Her-2/neu蛋白的表达.结果 免疫组化法检测显示,UPSC患者Her-2/neu蛋白阳性表达率为36.1%(13/36), Ⅰ型子宫内膜样腺癌患者为6.6%(9/136),两者比较,差异有统计学意义(P=0.000).显色原位杂交法检测显示,UPSC患者Her-2/neu基因高度扩增率为11.1%(4/36).显色原位杂交和免疫组化法检测的符合率为100%.36例UPSC患者中,手术病理分期Ⅲ～Ⅳ患者的Her-2/neu蛋白阳性表达率为50.0%(11/22),明显高于Ⅰ～Ⅱ期患者的14.3%(2/14,P=0.030);而不同肌层浸润深度、病理类型构成、病理分化程度及有无脉管侵犯、p53蛋白、雌激素受体(ER)、孕激素受体(PR)表达患者间Her-2/neu蛋白阳性表达率比较,差异均无统计学意义(P>0.05).单因素分析显示,Her-2/neu蛋白表达、肌层浸润深度和手术病理分期是影响UPSC患者预后的危险因素(P<0.05);多因素分析显示,Her-2/neu蛋白表达和肌层浸润深度是影响UPSC患者预后的独立危险因素(P<0.05).Her-2/neu蛋白阳性表达的13例患者中,8例子化疗者平均牛存时间(20个月)较5例未化疗者(42个月)短,但差异无统计学意义(P=O.370).结论 UPSC组织中Her-2/neu蛋白阳性表达与手术分期晚显著相关,Her-2/neu蛋白表达和肌层浸润深度是影响UPSC预后的独立危险因素.     

The serum pregnancy-specific β1-glycoprotein to betahuman chorionic gonadotrophin ratio as an index of prognosis in patients with choriocarcinoma

Summary. The ratio of serum pregnancy-specific β₁-glycoprotein (SP1) to the β-subunit of human chorionic gonadotrophin (β-hCG) before and after chemotherapy was measured in 12 patients with metastatic choriocarcinoma. The ratios before chemotherapy ranged between 0^.03 and 0^.75, with a mean value of 0^.34 (SD 0^.21). The ratio increased to over 1^.0 (1^.05–53^.3) after one or two courses of chemotherapy in seven of the 12 patients. These women achieved complete remission. In the other five patients who died of the disease due to drug resistance of the tumour, the ratio after chemotherapy was low (0^.04–0^.74) and tended to decline. These data suggest that the serum SPl/β-hCG ratio can be used to predict the prognosis of patients with choriocarcinoma.     

What is the correct management of stage i UPSC?

UPSC has been identified as a distinct variant of endometrial cancer and it has been reported to be associated with more aggressive behavior and a worse prognosis compared to endometrioid adenocarcinomas of the endometrium. Various studies have demonstrated survival rates of 15–51% for clinical stage I disease and 35–90% for surgical stage I/II disease. Aside from the very limited number of studies that incorporate comprehensive surgical staging, the majority of these reports used clinical parameters for staging or very limited surgical staging techniques and information.
A significant amount of controversy surrounds the optimal management of patients with stage I UPSC, and appropriate management of these patients has yet to be firmly established. The low incidence of this particular type of cancer, the variety of surgical interventions, and the wide variety of post-operative adjuvant therapies have made it extremely difficult to identify the optimal management of patients with UPSC. Prior to 2004, adjuvant treatment recommendations for surgical stage I UPSC were largely based on very small retrospective patient series (<20 patients), only a fraction of which included surgically staged patients. A recent publication reported the outcomes of surgical stage I UPSC patients from four institutions ⁽¹⁾ . Recurrence rates were lower than that published in previous studies, suggesting a potential benefit of comprehensive surgical staging in these patients. The risk of recurrence and mean overall survival were similar between surgical stage I UPSC patients who were managed conservatively versus those treated with adjuvant radiation therapy. Moreover, this study also suggests a potential benefit of adjuvant chemotherapy in these patients.     

Standard dose cisplatin with rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer

We have investigated the feasibility of a program of autologous peripheral blood stem cell (PBSC) harvesting and transplantation in patients with ovarian cancer. From four patients, PBSC was collected during hematopoietic recovery following aplasia induced by standard dose cisplatin 70 mg m⁻² with etoposide 500 mg m⁻² or adriamycin 40 mg m⁻² and cyclophosphamide 500 mg m⁻² plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) at a dose of 75 µg day⁻¹ given intracutaneously. In apheresed patients, we harvested an average of 2.31 × 10⁵ kg⁻¹ colony-forming unit granulocyte/macrophage (range 0–5.22) per cycle. Low hematologic toxicity was observed during the hematopoietic reconstitution of the four patients subjected to PBSC support with G-CSF (5 µg kg⁻¹ day⁻¹ given by continuous infusion) after high-dose chemotherapy (carboplatin 900 mg m⁻² and etoposide 900 mg m⁻²). The patients were not evaluable for a response because we performed consolidated high-dose chemotherapy. However, no evidence of recurrence has been observed 11.8 months (range 2–19) after high-dose chemotherapy. We can conclude that standard dose cisplatin in combination with etoposide or adriamycin and cyclophosphamide plus rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer.     

Serum CA125 assay at the time of relapse has no prognostic relevance in patients undergoing chemotherapy for recurrent ovarian cancer: a multicenter Italian study

The present retrospective study assessed the prognostic value of serum CA125 assay at relapse in 73 patients with recurrent epithelial ovarian cancer. At the time of relapse, serum CA125 levels ranged from 7 to 7000 U ml⁻¹. The 25%, 50% and 75% quantiles of CA125 levels were 76, 178 and 339 U ml⁻¹, respectively. Antigen values were >35 U ml⁻¹ in 67 (91.8%) of the 73 patients. Median time to recurrence was 16 months (range, 4–62 months). Serum CA125 levels at relapse were not related to site of recurrence, time to recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. Sixty patients received salvage chemotherapy at relapse. In these patients survival after recurrence was significantly related to time to recurrence ( 6 months vs < 6 months, P  = 0.0371; 12 months vs >12 months, P  = 0.0014; 16 months vs >16 months, P = 0.0001), but not to CA125 level at relapse (at any cut-off value for the antigen: 35, 76, 178 and 339 U ml⁻¹ ), site of recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. In conclusion, time to recurrence was the only variable predictive of further survival in patients undergoing salvage chemotherapy for recurrent ovarian cancer, whereas serum CA125 level at relapse had no prognostic relevance.     

Serum CA 125 as a tumor marker and the expression of c-erbB-2 oncogene in tubal malignancies

Serum CA 125 levels were evaluated in 26 patients with fallopian tube malignancies. CA 125 was elevated preoperatively in seven samples (median 178 U ml⁻¹ range 41–19021 U ml⁻¹), and postoperatively in eight of nine (89%) samples collected from patients with residual disease (median 109 U ml⁻¹ range 10–1883 U ml⁻¹) but only in one of seven (14%) samples from patients without residual disease (median 14, range 5–170 U ml⁻¹) ( P < 0.001). Changes in the serum CA 125 level during chemotherapy correlated with the clinical course of disease in 13 of 14 patients with a pre-chemotherapy serum CA 125 level> 35 U ml⁻¹. Nine patients with clinical remissions showed decreasing serum CA 125 levels, one with clinically stable disease showed decreasing levels and four with disease progression showed increasing levels. Serum CA 125 levels were measured in four patients before second-look laparotomy. Two of three with positive findings at laparotomy had elevated serum CA 125 levels whilst the third had a normal level. One patient with negative findings at second-look surgery had a normal CA 125 level. Disease relapse was associated with elevated serum CA 125 levels in nine of 10 patients (median 108 U ml⁻¹, range 27–38200 U ml⁻¹). Using immunohistochemical staining, none of the tumors showed positive cytoplasmic staining for c-erbB-2 (NEU) oncogene. This report shows that CA 125 is a reliable tumor marker for monitoring patients with cancer of the fallopian tube during active treatment and follow-up.     

Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu expression in ovarian cancer

OBJECTIVES: Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of cancer onset and progression. Abnormalities of epidermal growth factor receptor (EGFR) and Her-2/neu have been actively investigated in ovarian cancer and associated with unfavorable clinical outcome. The involvement of COX-2 in ErbB family pathways has been proposed. We investigated by immunohistochemistry the expression of COX-2, EGFR, and Her-2/neu in a series of advanced primary ovarian cancers. METHODS: The study included 76 consecutive stage IIIC-IV ovarian cancer patients with measurable disease after first surgery. Immunohistochemistry was performed on paraffin-embedded sections with rabbit antiserum against COX-2, murine monoclonal antibody (MoAb) 300G9 against Her-2/neu, and monoclonal antibody 108 against EGFR. RESULTS: No association among COX-2, EGFR, and HER-2/neu was found. COX-2 positivity was found in a statistically significant higher percentage of unresponsive cases (80.0%) than in patients responding to chemotherapy (35.7%) (P = 0.0008). The association between COX-2 positivity and poor chance of response to treatment was retained in multivariate analysis. In the subgroup of patients who underwent explorative laparotomy COX-2-positive cases showed a shorter overall survival (P = 0.049). CONCLUSIONS: COX-2 could represent a possible new marker of sensitivity to platin-based chemotherapy in ovarian cancer. The lack of association of COX-2 with EGFR or Her-2/neu suggests that the ability of COX-2 to predict tumor sensitivity to chemotherapy is not dependent on EGFR or Her-2/neu status and could be independently associated with prognosis. In this context, the availability of agents able to specifically interfere with COX-2, Her-2/neu, or EGFR tyrosine kinase is of potential interest.     

High-dose epirubicin in patients with advanced or recurrent uterine sarcoma

Twenty patients with advanced or recurrent uterine sarcoma who had not received prior chemotherapy, were treated with epirubicin 120 mg m⁻² intravenously every 3 weeks. Four patients (20%) achieved complete response (pathologically confirmed in three cases) and three (15%) achieved partial response. The overall response rate was 35% (95% CI: 15–59). no response was observed for pelvic lesions in previously irradiated areas. Three patients (15%) exhibited stable disease, while 10 (50%) had progressive disease. The median number of courses was six in responders and two in non-responders. The median survival was 48 months (range 19–50+ months) in responders and 6 months (range 2–18 months) in non-responders. Adverse effects consisted primarily of myelosuppression, nausea and vomiting. No patients experienced life-threatening toxicity. High-dose epirubicin appears to be active in patients with advanced or recurrent uterine sarcoma.     

Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization

Abstract. Kurata H, Takakuwa K, Tsuneki I, Aoki Y, Tanaka K. Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization.
The purpose of this study was to determine the efficacy of paclitaxel in combination with cisplatin and granulocyte-colony stimulating factor (G-CSF) for mobilization of peripheral blood progenitor cells (PBPC). Twenty-seven patients with gynecological cancer received paclitaxel and cisplatin (TP, n = 9) or other platinum-based chemotherapy ( n = 18) (etoposide and cisplatin [ n = 5]; cyclophosphamide, adriamycin, and cisplatin [ n = 8]; or pepleomycin, etoposide, and cysplatin [ n = 5]). Each combination was followed by G-CSF. The mean number of colony-forming unit granulocyte macrophage (CFU-GM)/kg and CD34⁺ cells/kg collected per cycle was 1.2 × 10⁵ and 0.8 × 10⁶ after the TP regimen, compared with 2.6 × 10⁵ ( P < 0.05) and 2.0 × 10⁶ for patients who received other platinum-based chemotherapy. The CFU-GM target yield (≥1.0 × 10⁵/kg) was achieved in 56% and 83% patients in the TP and comparison group, respectively. With the TP regimen, a younger age (≤50 years of age) and fewer prior chemotherapy cycles (≤2) were associated with the CFU-GM targeted yield (<0.05). In conclusion, TP mobilized PBPC less effectively than other platinum-based chemotherapy. Therefore, the TP regimen may need to be changed to another appropriate regimen when PBPC mobilization is planned for high-dose chemotherapy in gynecological cancer patients.     

Neoadjuvant chemotherapy with cisplatin, ifosfamide and 5-fluorouracil in the treatment of locally advanced cervical cancer

Abstract. Etcheverry MG, Marantz A, Saine M, Litovska S, Lewi D, Cecchin G, Nuñez de Pierro A. Neoadjuvant Chemotherapy in the treatment of locally advanced cervical cancer.
The objective of this study was to evaluate clinical and histological response, resectability, and survival in patients with cervical epidermoid carcinoma stage IB2 to IIIB with the use of neoadjuvant chemotherapy followed by radical surgery and/or radiation therapy. Between September 1989 and February 1996, 53 patients were admitted to this study. They were given three cycles of cisplatin 30 mg/m²/day, 5-fluorouracil 500 mg/m²/day, ifosfamide 2000 mg/m²/day i.v., and mesna 400 mg/m²/day i.v. at hour 0 and 400 mg/m² at hours 4 and 8 during three days every 21–28 days. We evaluated 47 patients. Global clinical response obtained was 85%{95% (CI), 75–97%, CR in 14 patients (30%) and PR in 26 patients (55%)}. Twenty-three patients underwent surgery. Six patients (13%) had a complete histological response. Median follow-up was 42 months (5–96). In resected patients, with a median follow-up of 57 months (5–96), the estimated five-year disease-free survival was 78%. Global survival estimated to 60 months was 83% for stage IB2, 70% for IIB, and 20% for IIIB. This mode of therapy offers a new option to improve survival in locally advanced cervical cancer. Randomized trials are required in order to establish a definitive role for this therapeutic strategy.     

The antiobesity drug Orlistat induces cytotoxic effects, suppresses Her-2/neu (erbB-2) oncogene overexpression, and synergistically interacts with trastuzumab (Herceptin™) in chemoresistant ovarian cancer cells

Abstract.   Menendez JA, Vellon L, Lupu R. The antiobesity drug Orlistat induces cytotoxic effects, suppresses Her-2/neu (erbB-2) oncogene overexpression, and synergistically interacts with trastuzumab (Herceptin^™) in chemoresistant ovarian cancer cells. Int J Gynecol Cancer 2006; 16: 219–221.     

Long term survival of patients with advanced ovarian cancer treated with intraperitoneal radioimmunotherapy

Abstract. Epenetos AA, Hird V, Lambert H, Mason P, Coulter C. Long term survival of patients with advanced ovarian cancer treated with intraperitoneal radioimmunotherapy.
Purpose: To determine the long term survival of patients with advanced ovarian cancer treated with radioimmunotherapy following cytoreductive surgery and platinum based chemotherapy.
Patients and Methods: Eligibility criteria included patients with histological evidence of ovarian cancer stages IC-IV following completion of conventional platinum containing chemotherapy. Of 52 patients entered into the study, 31 had residual disease following standard chemotherapy and 21 patients had achieved complete remission. Treatment consisted of one intraperitoneal administration of 25 mg of monoclonal antibody HMFG1 labelled with 18 mCi/m² of ⁹⁰Y. Survival was the primary end-point.
Results: In the group of 21 patients who had achieved complete remission following surgery, conventional chemotherapy and intraperitoneal radioimmunotherapy, the median survival has not been reached with a maximum follow-up of 12 years. Survival at greater than 10 years is 78%.
Conclusion: This study suggests that a substantial proportion of patients who achieve complete remission with conventional therapy can achieve a long-term survival benefit when treated with intraperitoneal radioimmunotherapy using HMFG1 labelled with ⁹⁰Y.     

Her-2/neu expression in ovarian cancer: pre- and postexposure to platinum chemotherapy

OBJECTIVE: Our objective was to determine if the level of Her-2/neu expression in advanced ovarian cancer changed after platinum-based chemotherapy. METHODS: Tissue samples from 43 patients who had surgery for ovarian cancer between 1991 and 2001 at the Mayo Clinic were stained for Her-2/neu expression using the DAKO kit and reviewed independently by two pathologists. Patient charts were reviewed for demographic data, clinical course, chemotherapy, and survival times. RESULTS: Her-2/neu expression was 0 in 30 patients (69.76%), 1+ in 12 patients (27.9%), and 3+ in 1 patient (2.32%) before chemotherapy. After platinum chemotherapy, Her-2/neu expression changed from 0 to 1+ in 7 patients, from 1+ to 0 in 4 patients, 0 to 2+ in 1 patient, and 1+ to 2+ in 2 patients and no change was seen in 29 patients. Both pathologists agreed in all instances when the score was 0 or 1+ and disagreed in two instances between a negative and a weakly positive staining. CONCLUSIONS: Our findings indicate a low level of overexpression of Her-2/neu at the time of primary diagnosis of epithelial ovarian cancer. Relapsing tumors show no significant change in the intensity of Her-2/neu expression after platinum-based chemotherapy. Further prospective studies are needed to confirm these findings and to ascertain whether platinum chemotherapy indeed has no effect on Her-2/neu expression.     

Carboplatin and etoposide as first-line chemotherapy in advanced epithelial ovarian cancer

Carboplatin and etoposide are chemotherapeutic agents active in ovarian cancer, previously proved to have a synergistic activity in animal models. The objective of this phase II study was to determine the feasibility and the efficacy of the combination of carboplatin and etoposide in previously untreated patients with advanced epithelial ovarian cancer.
Carboplatin, 400 mg m⁻² day 1, and etoposide, 100 mg m⁻² days 1–3 every 4 weeks were administered to 28 patients with advanced stage (III–IV) ovarian cancer and a performance status 0–2 (ECOG scale), as a firstline chemotherapy.
Twenty-three patients were evaluable for response; 15 (65%) (95% CI: 45–81%) responded, 10 (43%) (95% CI: 25–63%) with clinical complete response. Pathologic complete response demonstrated during postchemotherapy laparotomy was noted in 5/23 (22%) (95% CI: 9–42%) patients. The median progression-free interval was 8.5 months, and median survival was 19.5 months. Toxicity, mainly hematologic, was severe. Nine (32%) patients experienced at least one episode of leucopenic fever, which consequently led to toxic deaths in two (7%) patients.
The relatively low response and survival rates with increased toxicity rate are disappointing.     

Topotecan in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma

Abstract.   Piura B, Rabinovich A. Topotecan in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma. Int J Gynecol Cancer 2005; 15: 612–617.
Topotecan has demonstrated antitumor activity in heavily pretreated patients with ovarian carcinoma. This report examines the activity and toxicity of topotecan in 29 heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma. Topotecan 1.5 mg/m² was administered intravenously on days 1–5, every 21 days. It was second-line chemotherapy in 6 (20.7%) patients, third-line in 15 (51.7%), fourth-line in 4 (13.8%), fifth-line in 3 (10.3%), and seventh-line in 1 (3.4%). Median dose intensity was 1.667 mg/m²/week, and median relative dose intensity was 0.67. Disease complete response was observed in 5 (17.2%) patients, partial response in 1 (3.4%), stable disease in 12 (41.4%), and progressive disease in 11 (37.9%). CA-125 complete response was observed in 3 (10.3%) patients, partial response in 11 (37.9%), stable level in 5 (17.2%), and progressive level in 9 (31%), and no data were available in 1 (3.4%) patient. Toxicity was mainly hematologic: grade 3–4 neutropenia was observed in 20 (69%) patients, grade 3–4 leukopenia in 12 (41.4%), grade 3–4 thrombocytopenia in 9 (31%), and grade 3–4 anemia in 2 (6.9%). It is concluded that topotecan has considerable activity and noncumulative hematologic toxicity in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma.     

Evaluation of serum CA 125 level as a tumor marker in borderline tumors of the ovary

Serum CA 125 was evaluated as a tumor marker in 85 patients with borderline ovarian tumors. Serum CA 125 levels were elevated preoperatively in 18 of 20 (90%) samples (median 66, range 5–272 U ml⁻¹). Preoperative serum CA 125 levels did not correlate to FIGO stage. Preoperative serum CA 125 levels were elevated in seven of nine (78%) with serous tumors (median 131, range 5–272 U ml⁻¹) and in all 11 with mucinous tumors (median 62, range 41–157 U ml⁻¹). There was no significant difference in the CA 125 levels between these two histologic types. Postoperative serum CA 125 levels, measured 3–6 weeks after primary laparotomy, were significantly lower than the preoperative ones ( P < 0.001). No difference in the postoperative CA 125 levels was found between those with and those without residual disease after surgery. Postoperative serum CA 125 levels were elevated in eight of 60 (13%) without residual tumor. None of these had relapsed at the time of analysis (26–87 months after surgery). Serum CA 125 levels tended to correlate with disease evolution during chemotherapy. Two with disease remissions had falling levels, one with stable disease had falling level and one with disease progression had rising level. Serum CA 125 samples were obtained before second-look laparotomy in seven patients. Two with negative findings at second-look had normal levels. Of five with positive findings at laparotomy only two had elevated serum CA 125 levels. Disease relapse was associated with elevated serum CA 125 levels in only one of six patients.     

Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer characterized by a high recurrence rate and a poor prognosis. Prior studies evaluating treatment of UPSC have been limited by small numbers of patients and inclusion of partially staged patients. The purpose of this study was to evaluate the efficacy of adjuvant platinum-based chemotherapy and vaginal cuff radiation in a large cohort of surgical stage I UPSC patients. METHODS: We retrospectively reviewed 74 stage I patients with UPSC who underwent complete surgical staging at our institution between 1987 and 2004. RESULTS: Stage IA patients were divided into two groups: patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease) and patients with cancer in the hysterectomy specimen (defined as residual uterine disease). Stage IA patients with no residual uterine disease had no recurrences, regardless of adjuvant therapy (n = 12). Stage IA patients with residual uterine disease who were treated with platinum-based chemotherapy had no recurrences (n = 7). However, 6 of 14 (43%) stage IA patients with residual uterine disease who did not receive chemotherapy recurred. The 15 patients with stage IB UPSC who received platinum-based chemotherapy had no recurrences but 10 of the 13 (77%) stage IB patients who did not receive chemotherapy recurred. One of the 7 patients with stage IC UPSC who received platinum-based chemotherapy recurred and 4 of the 5 (80%) stage IC patients who did not receive chemotherapy recurred. Overall platinum-based chemotherapy was associated with improved disease-free survival (P < 0.01) and improved overall survival (P < 0.05) in patients with stage I UPSC. None of the 43 patients who received radiation to the vaginal cuff recurred locally, but 6 of the 31 (19%) patients who were not treated with vaginal radiation recurred at the cuff. CONCLUSIONS: Platinum-based chemotherapy improves the disease-free and overall survival of patients with stage I UPSC and vaginal cuff radiation provides local control. Stage IA UPSC patients with no residual uterine disease can be observed but concomitant platinum-based chemotherapy and vaginal cuff radiation (referred to as chemoradiation) should be offered to all other stage I UPSC patients.     

The effect of adjuvant chemotherapy versus whole abdominopelvic radiation on the survival of patients with advanced stage uterine papillary serous carcinoma

OBJECTIVES: To compare the outcomes of stage III and IV uterine papillary serous carcinoma (UPSC) patients treated with platinum-based chemotherapy (PC) versus whole abdominopelvic irradiation (WAPI) after optimal cytoreductive surgery. METHODS: Surgically staged patients with advanced stage UPSC diagnosed between 1981 and 2002 were identified from tumor registry databases at four hospitals. Survival analyses and predictors of outcome were analyzed using Kaplan-Meier methods. RESULTS: Of the 40 patients with advanced UPSC (median age: 64.5), 84% were Caucasian, 8% were African American, and 8% were Asian. The majority of patients (85%) presented with vaginal bleeding. Twenty-seven had stage III and 13 had stage IV disease. All patients were optimally debulked; 21 patients received adjuvant PC while 19 underwent WAPI. The median follow-up was 27 months (range: 5-209). The 3-year overall survival (OS) and progression-free survival (PFS) for the patients with stage III disease were 49% and 37% compared to 37% and 31% in those with stage IV disease (P = 0.23 for OS; P = 0.41 for PFS). Women who received PC had a 3-year OS and PFS of 43% and 31% compared to 45% and 41% in those receiving WAPI, respectively (P = 0.40 for OS; P = 0.84 for PFS). CONCLUSION: Platinum-based chemotherapy or whole abdominopelvic irradiation resulted in similar survival in this series of women with optimally cytoreduced UPSC. Given the overall poor prognosis of these patients, new treatment modalities are warranted.     

Carboplatin and chlorambucil combination chemotherapy as treatment for patients with ovarian cancer

Fifty-six patients with ovarian cancer (three stage IC, nine stage II, 33 stage III and II stage IV) were treated with carboplatin 350 mg m⁻² i.v. day 1 and chlorambucil orally 0.15 mg kgm⁻¹ days 1–7 inclusive, repeated every 28 days for eight courses. The regimen was well tolerated and was virtually free of nephro- and neurotoxicity. Grade III or IV hematology toxicity occurred in 18 patients but only 31 or 330 courses administered were delayed. Of 40 assessable patients eight achieved a clinical/radiologic complete response and 17 a clinical/radiologic partial response. Actuarial survival at 50 months was 65% for stage II patients, 27% for stage III patients and no stage IV patients survived beyond 20 months. Forty-two per cent of patients with residual disease less 2 cm survived 50 months, compared with 44% of patients with moderate volume (2–5 cm) residual disease and 6% of patients with bulk residual disease. This is an active, well tolerated regimen. However, only patients with small volume residual disease have a significant chance of prolonged survival.     

The treatment of uterine papillary serous carcinoma (UPSC): are we doing the right thing?

Abstract. Tay EH, Ward BG. The treatment of uterine papillary serous carcinoma (UPSC): are we doing the right thing?
In an earlier study ⁽¹⁾ of 21 patients with uterine papillary serous carcinoma (UPSC), Ward et al . found a poor 3-year survival, even for patients with surgically documented localized disease, and a high rate of recurrence outside the field of treatment. Eight years later, we performed a retrospective study on 67 patients who were treated initially by surgery, which included the 21 patients previously reported, to evaluate any changes in the management approach since 1990 and its impact on the survival of such patients. The clinical characteristics of patients treated before and after 1990 were similar. However, after 1990, more patients had omentectomy and complete surgical staging (42% vs. 17%); chemotherapy was more widely used (63% vs. 33%); all chemotherapies were platinum-based regimens and less radiotherapy was administered (47% vs. 83%). The overall 3-year survival was 43% and 5-year survival was 35%, with a median survival period of 31 months. There was no significant difference in the survival outcome between patients managed before and after 1990, after adjusting for stage and spread of disease. Based on the results of this retrospective study, it appears that the current treatment strategy has not resulted in an improvement in the survival of patients with UPSC.