BACKGROUND:This study reviews the experience at the University of Texas M.D. Anderson Cancer Center with elderly patients treated for advanced epithelial ovarian cancer with cisplatin-based combination chemotherapy.METHODS:From 1978 through 1988, 215 patients with Stage III or IV, Grade 2 or 3 epithelial ovarian cancer were entered onto one of three consecutive trials involving cisplatin-based combination chemotherapy. The treatment plans were as follows: Trial 1: 12 cycles of cisplatin-melphalan (75 patients); Trial 2: 12 cycles of cisplatin-cyclophosphamide (49 patients); and Trial 3: 6 cycles of cisplatin-cyclophosphamide (91 patients). End-points of analysis included the effect of age on other prognostic factors, clinical response rate, surgical response rate, toxicity, progression-free survival, and survival.RESULTS:Of the entire study group, 57 patients (27%) were 65 years of age and older at diagnosis. There was no effect of age on FIGO stage or histologic grade distribution, but 61% of patients younger than 65 years of age had residual tumors less than or equal to 2 cm compared with only 33% of patients 65 years of age and older (P = 0.00027). There were no differences between the two age groups with respect to response rates, recurrence rate after negative second-look surgery, toxicity, or progression-free survival. Patients in the younger than 65 years of age group, however, had a significantly longer median survival time than those 65 years of age and older (30 versus 19 months, respectively) (P = 0.0038).CONCLUSIONS:This analysis suggests that elderly patients are more likely to begin chemotherapy with bulky residual disease and to have a significantly shorter survival time than their younger counterparts.

Purpose: To look for possible associations between measurements of DNA index (DI), S-phase fraction (SPF), and tumor, heterogeneity (TH) using flow cytometry and overall survival for patients with invasive cervical carcinoma treated with definitive irradiation.Methods and Materials: A total of 57 patients with International Federation of Obstetrics and Gynecology Stages IB2 through IVB cervical carcinomas treated with definitive radiotherapy with or without concurrent chemotherapy were enrolled into this registry study that involved flow cytometric analysis of fresh tissue from each cervical cancer obtained by pretreatment biopsy. These specimens were evaluated for DNA aneuploidy (DI <= 51.5 vs. > 1.5), SPF (<= 15% vs. > 15%), and TH (uniploid vs. multiploid).Results: In these analyses 27 of the patients were treated in Radiation Therapy Oncology Group protocol 9001, and an additional 30 were offered chemoradiation at a single institution. Forty-one patients had DI <= 1.5 and 16 DI >1.5. Twenty-nine patients had SPIT : 15%, 26 >15%, and 2 had no determinable SPF. Forty-three patients had uniploid and 14 multiploid tumors. The 4-year estimated overall survival rate for the entire study cohort was 62% (95% confidence interval 48%-74%). With a median follow-up of 3.7 years, there were no observable associations by univariate analysis for DI, SPF, or TH concerning patient survival.Conclusions: There were no statistically significant associations among DI, SPF, or TH and patient outcome. Additional studies are indicated to identify tumor biomarkers that could predict patients at risk for disseminated disease. (c) 2008 Elsevier Inc.

PURPOSE:To report mature results of a randomized trial that compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) in women with locoregionally advanced carcinomas of the uterine cervix.PATIENTS AND METHODS:Four hundred three women with cervical cancer were randomly assigned to receive either EFRT or CTRT. Patients were eligible if they had stage IIB to IVA disease, stage IB to IIA disease with a tumor diameter > or = 5 cm, or positive pelvic lymph nodes. Patients were stratified by stage and by method of lymph node evaluation.RESULTS:The median follow-up time for 228 surviving patients was 6.6 years. The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). There was an overall reduction in the risk of disease recurrence of 51% (95% CI, 36% to 66%) for patients who received CTRT. Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT (P <.0001); 116 patients with stage III to IVA disease had better disease-free survival (P =.05) and a trend toward better overall survival (P =.07) if they were randomly assigned to CTRT. The rate of serious late complications of treatment was similar for the two treatment arms.CONCLUSION:Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.

Purpose To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). Results Hypothesis. A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. Patient Population. The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. Intervention. Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. Outcomes. An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting. Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. Trial Design. The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer–specific survival; the time to development of metastatic disease is an alternative. Conclusion Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

Purpose/Objective: To report mature results of a randomized trial that compared extended field radiotherapy (EFRT) with chemoradiation (CT-RT) in women with loco-regionally advanced carcinomas of the uterine cervix. Materials/Methods: Between 1990 and 1997, 403 women were randomized to receive either EFRT (45 Gy to the pelvis and paraaortic nodes followed by low dose-rate intracavitary radiation (ICRT)) or CT-RT (45 Gy pelvic RT and ICRT with 3 cycles of concomitant 5-FU and cisplatin). Patients with cervical cancer were eligible if they had stages IIB–IVA, stages IB2–IIA with tumor diameter ≥ 5 cm, or positive pelvic lymph nodes. Paraaortic lymph nodes (PAN) were evaluated with either lymphangiogram or lymphadenectomy. To achieve balance between the treatment arms, patients were stratified by stage (IB–IIB and III-IVA) and by method of lymph node evaluation. Overall, 96 patients (25%) had positive pelvic lymph nodes and 118 (30%) had stages III-IVA disease. For patients with stages IB–IIA the median tumor diameter was 6 cm. Median follow-up of surviving patients was 5.8 years. Results: Of 403 patients randomized, 195 and 194 could be evaluated in the EFRT and CT-RT arms, respectively. Overall 5-yr survival rates for patients treated with EFRT and CT-RT were 52% and 72%, respectively (p < 0.0001). Disease-free survival rates were 43% and 67%, respectively (p < 0.0001) and pelvic recurrence rates were 34% and 18%, respectively (p < 0.0001). The rates of PAN recurrence were not significantly different for patients treated with EFRT and CT-RT (4% and 7%, respectively; p = 0.15). However, other distant metastases were significantly more frequent for patients treated with EFRT (31% vs. 18%, p = 0.001). Although the study was not powered to detect a treatment difference within the stratified subgroups, of the 272 patients with stages IB–IIA those treated with CT-RT had a significantly better OS than those treated with EFRT (78% vs. 55%, p < 0.0001); of the 117 patients with stages III-IVA, there was a trend toward better OS for those treated with CT-RT (59% vs. 47%, p = 0.066). The 5-yr rates of late grade 3 or higher treatment-related toxicity were comparable for patients treated with EFRT and CT-RT (12% and 14%, respectively; p = 0.65). Conclusions: Mature analysis confirms that the addition of 5-FU and cisplatin to radiation therapy significantly improved the survival rate of women with locally advanced cervical cancer, decreasing both local and distant recurrences without significantly increasing the rate of late treatment-related side effects.

OBJECTIVE:The purpose of this study was to review our experience with continent urinary diversions in patients with gynecologic malignancies and evaluate the presentation and management of early and late complications.METHODS:A retrospective chart review was performed of all patients who underwent a continent urinary diversion on the Gynecologic Oncology Service at The University of Texas M. D. Anderson Cancer Center during the period January 1988 to March 2001. We analyzed our data to evaluate potential risk factors for complications. Renal status, conduit integrity, and overall patient outcomes were also studied.RESULTS:We identified 40 patients who underwent a continent urinary diversion using an ileocolonic segment (Miami pouch technique). All patients had a history of gynecologic malignancies. The median age at the time of the procedure was 50 years (range 24 to 76 years), and the median weight was 69.6 kg (range 47 to 125 kg). A total of 39 patients (98%) had a history of radiotherapy. Continent urinary diversion was performed as part of an anterior pelvic exenteration in 12 patients (30%), in conjunction with a total pelvic exenteration in 18 patients (45%), and as the main procedure in 10 patients (25%). The median estimated blood loss was 2100 ml (range 200 to 8500 ml). The median length of hospitalization was 19.5 days (range 7 to 56 days). A total of 24 patients (60.0%) had a postoperative complications unrelated to the reservoir. Complications directly related to the continent urinary diversion were seen in 26 (65.0%) of 40 patients. None of the patients in this study group developed chronic renal failure, and there were no perioperative deaths. At last evaluation, 36 (90%) of 40 patients reported normal continent conduit function.CONCLUSIONS:Continent urinary diversion using an ileocolonic segment is a reasonable alternative to the ileal and transverse colon conduit in bladder reconstruction in patients undergoing radical pelvic surgery. The routine use of postoperative total parenteral nutrition, the chronic use of antibiotics after discharge from the hospital, and the routine use of imaging studies remain controversial. In this group of patients, the majority of complications may be successfully managed conservatively.

OBJECTIVE:To study reproductive function and disease outcome in women with borderline ovarian tumors who were treated with conservative surgery. METHODS:Patients with borderline ovarian tumors were identified from institutional databases. Patients were eligible if they had pathologically confirmed borderline ovarian tumors, no prior sterilization, no history of radiation therapy, retained their uterus and ovarian tissue, and were younger than age 45. Information was acquired by retrospective medical record review and patient interview. RESULTS:Forty-three patients met the eligibility criteria. The median age was 25 years, with a range of 15-39 years. Twenty-six patients had serous tumors, and 17 had mucinous tumors. Fifteen had stage I disease, three had stage III, and 25 were unstaged. Follow-up was available for all patients (median, 5.7 years). Twenty-nine remained disease-free, and 14 developed a new primary lesion/recurrence, with a median time to recurrence of 39.3 months. Recurrence was more frequent in patients treated with ovarian cystectomy than in those treated with oophorectomy alone (58% compared with 23%) (P <.04). After treatment, 29 of 36 patients (81%) retained normal menstrual cycles, and 12 of 24 patients attempting pregnancy conceived 25 pregnancies. Most patients were highly satisfied with conservative surgery. CONCLUSION:Conservative surgery remains a therapeutic option in selected patients with borderline ovarian tumors. Although the rate of new lesion/recurrence is relatively high, especially in those treated with ovarian cystectomy, mortality from cancer remains low. Many patients who desire pregnancy are able to conceive and deliver healthy offspring after conservative surgery.

OBJECTIVE:The aim of this study was to develop a surveillance program that optimizes clinical outcome following primary treatment of women with cervical cancer.METHODS:The records of 1096 patients with FIGO stage IB cervical cancer treated from 1983 to 1993 were retrospectively reviewed. Recurrence was analyzed by site, presence or absence of symptoms, method of detection, and survival. Univariate and multivariate analyses using a Cox proportional hazards model were performed.RESULTS:One hundred thirty-three patients (13%) developed recurrent disease. Of these, 114 were symptomatic and 19 were asymptomatic at the time of recurrence. Thirty-seven patients recurred in the central pelvis, 21 each in the lung or pelvic wall, 22 in nodes, and 35 in other sites. The median disease-free interval was 17 months for symptomatic patients and 16 months for asymptomatic patients. The median survival from initial diagnosis was 31 months for symptomatic and 83 months for asymptomatic patients (P = 0.001). The median survival from recurrence was 11 months for symptomatic and 42 months for asymptomatic patients (P < 0.001). Multivariate analysis revealed that symptom status at time of recurrence was a significant predictor of survival, even when known prognostic factors were considered (P < 0.001). All asymptomatic pelvic recurrences were diagnosed by pelvic exam; all asymptomatic pulmonary recurrences were detected by chest radiographs. Pap smears did not detect a single asymptomatic recurrence.CONCLUSIONS:Posttherapy surveillance programs are directed toward asymptomatic patients in whom early detection of recurrence may impact survival. These data indicate that a subset of women may benefit from surveillance. A model for surveillance is proposed.

Purpose: To evaluate the long-term results of continuous infusion intra-arterial 5-fluorouracil (CI IA 5-FU) given with concurrent pelvic radiotherapy (RT) for FIGO stage IIIB-IVA carcinoma of the cervix.Methods and Materials: Between 1965 and 1974, 27 patients with extensive FIGO Stage IIIB (22 patients) or Stage IVA (5 patients) squamous cell carcinoma of the cervix were treated with CI IA 5-FU and RT, Twenty-one patients (78%) had bilateral pelvic wall involvement, 25 (93%) had massive tumors (greater than or equal to 8 cm in diameter), 7 (27%) had involvement of the lower one-third of the vagina, and 15 (56%) presented with hydronephrosis. All patients underwent routine clinical staging, transperitoneal para-aortic lymph node dissection, and bilateral hypogastric artery catheter placement. 5-FU was continuously infused at a dose rate of 10 mg/kg/day on Days 1-15 of RT, The median dose of 5-FU was 376 mg/m(2)/day (range 270-692), All patients received concurrent pelvic RT to a median dose of 50 Gy at 2.0 Gy per fraction. Only 4 patients received intracavitary RT. The median follow-up of surviving patients was 190 months.Results: The overall 5-year survival rate was 37%. For the 22 patients with FIGO Stage IIIB disease, the 5-year survival rate was 41%. The survival rate for 18 patients treated with only external beam radiation and chemotherapy for Stage IIIB disease was 33%. Four of 10 patients treated with only 50 Gy of external beam radiation and CI IA 5-FU were long-term survivors. Acute complications, including hematologic toxicity and skin reactions, were severe, with 1 death from neutropenic sepsis, Severe late complications were only observed in patients treated with greater than or equal to 60 Gy of external beam radiation,Conclusions: While this series is small, the fact that 4 patients with massive Stage IIIB tumors survived after a total radiation dose of only 50 Gy suggests that RT with CI IA 5-FU deserves further study. Modifications in dose, technique, and route of administration should reduce toxicity, and the addition of intracavitary RT should improve the local effectiveness of combined treatment, (C) 1999 Elsevier Science Inc.

BACKGROUND AND METHODS:We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group.RESULTS:Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P<0.001). The rates of both distant metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group.CONCLUSIONS:The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer.

BACKGROUND, The primary purpose of this study was to establish the maximum tolerated dose (MTD) of intravenous melphalan in combination with paclitaxel and cisplatin plus granulocyte-colony stimulating factor (G-CSF) in patients with suboptimal advanced epithelial ovarian carcinoma or primary peritoneal carcinoma.METHODS, Patients with suboptimal (>2 cm residual tumor) Stage III or Stage IV at 135 mg/m(2) and 75 mg/m(2), respectively, and the dose of intravenous melphalan was escalated in consecutive cohorts of 3-6 patients depending on toxicity. The planned dose escalation levels of melphalan were 6 mg/m(2), 10 mg/m(2), and 14 mg/m(2). In the second stage of the study, the doses of cisplatin and melphalan were fixed at 75 mg/m(2) and the MTD level, respectively, and the dose of paclitaxel was escalated. The planned dose escalation levels of paclitaxel were 150 mg/m(2), 175 mg/m(2), 200 mg/m(2), 225 mg/m(2), and 250 mg/m(2). G-CSF was administered for 12-19 days with each cycle, and cycles were repeated every 4 weeks for a total of 6 cycles. Other end points included clinical or surgical response, progression free survival, and survival.RESULTS. Between January 1993 and May 1996, 34 women with untreated advanced stage epithelial ovarian carcinoma or primary peritoneal carcinoma were treated with 192 cycles of therapy. The MTD of melphalan was 10 mg/m(2), with the dose-limiting toxicity being thrombocytopenia. Paclitaxel was escalated to a dose level of 200 mg/m(2) with a toxicity rate of < 33%. The clinical response rate was 80% in 29 patients with measurable disease. Of 11 patients who underwent second-look surgery, 5 (45%) had a surgical pathologic complete response. The median progression free survival was 16.8 months and the median survival was 32.8 months.CONCLUSIONS. The combination of intravenous melphalan, paclitaxel, and cisplatin was found to have acceptable toxicity and good activity. A Phase II study of this combination appears to be warranted. (C) 1999 American Cancer Society.

PURPOSE To evaluate the efficacy and toxicity of intravenous vinorelbine as single-agent chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Between August 1993 and July 1995, 35 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Patients had received no prior therapeutic chemotherapy. The initial dose of vinorelbine 30 mg/m2 was administered as a weekly intravenous infusion. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group (GOG) and World Health Organization criteria, respectively. RESULTS Thirty-three of 35 patients were assessable for response and 35 of 35 for toxicity. The overall response rate was 18% (one complete response [CR], five partial responses [PR]). The mean response duration was 5.2 months and the median survival from treatment for all patients was 11.0 months. The major toxicity was leukopenia, with 61% of patients who had grade 3 or 4. Gastrointestinal and neurotoxicity were infrequent and mild. CONCLUSION Vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Further studies of combination regimens with this agent are justified in this patient population.

BACKGROUND. The authors conducted this study to update their experience with patients who have ovarian serous borderline tumors with noninvasive peritoneal implants, with the objectives of gaining additional insight into the biologic behavior of these tumors and understanding better the effects of postoperative treatment.METHODS. Seventy-three patients who had ovarian serous borderline tumors with noninvasive peritoneal implants were identified in a retrospective review. Major end points selected for analysis were surgicopathologic response, time to relapse, type of relapse, progression free survival, and overall survival. Univariate and multivariate regression analyses were also performed.RESULTS. The median follow-up time was 10.3 years. Of 20 patients with macroscopic residual disease at completion of initial surgery who subsequently underwent second-look surgery, 3 (15%) had a response to chemotherapy. Twenty-two of 73 patients (30%) either developed progressive disease or had a relapse. The median time from the date of diagnosis to relapse was 7.1 years. Tissue was available from 20 of the 22 patients who had a relapse; 14 (70%) had invasive low grade serous carcinomas, and 6 (30%) had recurrent borderline tumors. Age was the only factor studied that had a significant influence on survival (P = 0.03). In both univariate and multivariate proportional hazards models, age and residual disease were found to be of borderline significance in predicting cancer specific survival.CONCLUSIONS. Approximately 30% of patients who have ovarian serous borderline tumors with noninvasive peritoneal implants will develop progressive or recurrent tumors, most commonly serous carcinomas. The presence of macroscopic residual disease appears to be a predictor of disease free survival. In this study, however, the authors were unable to elucidate the role of postoperative therapy or determine criteria for selecting patients for such therapy. Cancer 1998;83:2157-63, (C) 1998 American Cancer Society.

Purpose. To determine the toxicity and activity of intravenous vinorelbine given daily for 3 consecutive days every 3 weeks in patients with platinum-resistant epithelial ovarian cancer.Patients and methods. Between September 1994 and October 1995, 23 women with refractory epithelial ovarian cancer were entered onto this phase I study. All patients had measurable disease and platinum-resistant tumor, and prior therapy was limited to a maximum of two prior regimens. Nineteen (83%) were assessable for toxicity and 20 (87%) were assessable for response. Vinorelbine was administered intravenously daily for 3 consecutive days; this was repeated every 21 days. The starting dose was 20 mg/m(2) daily x3, with dose escalation by 5 mg/m(2) daily x3. Dose-limiting toxicity (DLT) was defined as grade 4 granulocytopenia for >3 days, grade 4 thrombocytopenia, neutropenic fever, or grade 3 or greater nonhematologic toxicity. The maximal tolerated dose (MTD) was defined as the highest dose level at which <50% of patients developed a DLT, Once the MTD of vinorelbine without granulocyte colony-stimulating factor (filgrastim) support was defined, dosing was begun at the MTD level and administration of 5 mu g/kg filgrastim was initiated on day 4 and continued until WBC counts reached >10,000/mu L. Clinical response, progression-free survival, and survival were also determined.Results. Nineteen patients evaluable for toxicity received a total of 135 cycles of vinorelbine, The major DLT was neutropenia. The MTD of vinorelbine without filgrastim support was established as 20 mg/m(2) daily x3. The MTD of vinorelbine with filgrastim support was established as 25 mg/m(2) daily x3. Of 20 patients evaluable for response, 2 patients (10%) had a complete response and 4 (20%) had a partial response, for an overall response rate of 30%,Conclusion. These results warrant further study of vinorelbine in patients with platinum-resistant epithelial ovarian cancer. However, further study of the daily x3 schedule may not be warranted because of failure to achieve higher weekly dose intensity and because of nonhematologic toxicity in the form of intense bone pain, (C) 1998 Academic Press.

PURPOSE To identify characteristics that predict response to chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Between January 1986 and May 1996, 190 chemotherapy-naive patients with advanced or recurrent squamous cell carcinoma of the cervix not amenable to curative radiation therapy or surgery were treated on 14 different chemotherapy protocols at M.D. Anderson Cancer Center. Patient's charts were retrospectively reviewed for patient demographics, tumor and treatment characteristics, and patterns of response and survival. RESULTS Of 190 patients, 22 had advanced or persistent disease and 168 had recurrent disease. Patients were treated with platinum-based (n=95) and non-platinum-based (n=95) regimens. The overall response rate was 20.0% (4.2% complete response; 15.8% partial response), with a median response duration of 4.8 months. Race, socioeconomic class, tumor stage and grade, mode of primary treatment, time from primary diagnosis to disease recurrence, initial performance status, and use of platinum-based therapy were not significant predictors of response. Age at time of chemotherapy (P=.001) and site of recurrence (P=.044) were significant determinants by multivariate analysis. Patients who were older were more likely to respond to therapy, and the response rate for patients in whom disease recurred outside the irradiated field was 25.2%, compared with a 5.3% response rate for patients with recurrent disease limited to a previously irradiated field. CONCLUSION The site of disease recurrence and patient age should be taken into account when designing chemotherapy trials and also when considering chemotherapy in the patient with recurrent cervix cancer.

OBJECTIVE To evaluate the efficacy and toxicity of prolonged oral etoposide as single agent chemotherapy in patients with advanced or recurrent carcinoma of the cervix. METHODS Between May 1991 and February 1993, 44 patients with advanced or recurrent carcinoma of the cervix were entered onto this study. Patients were eligible if they had received no more than two prior cytotoxic regimens. The initial dose of etoposide was 37.5 mg/m2 administered orally on a daily basis on days 1-21 of a 28-day cycle. Subsequent doses were unchanged, reduced, escalated, or omitted according to toxicity. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group criteria. RESULTS Forty-four patients were evaluable for response and toxicity. The overall response rate was 9.1% (2 CR, 2 PR). In patients with no prior chemotherapy the response rate was 4/25 compared to 0/19 for those who had prior therapy. The mean response duration was 2.7 months and the median survival from treatment for all patients was 7.7 months. The major toxicity was granulocytopenia, with 11% of patients having grade 3 or 4 toxicity. Gastrointestinal toxicity of some degree occurred in 11% of patients, and alopecia was universal. CONCLUSION Prolonged oral etoposide has limited activity in advanced or recurrent carcinoma of the cervix. Its use as palliative therapy for this disease is not indicated.

Objective: To evaluate the effectiveness of an outcomes-management program designed to provide high-quality patient care, generate data for outcomes research, and decrease costs in a managed-care environment.Methods: An outcomes-management program was launched in June 1994, based on the elimination of wasteful or ineffective therapies through the systematic development of practice guidelines and collaborative care paths, with concomitant definition of desired outcomes. Over 3 months, care paths were developed for our most common surgical procedures. A matched control outcomes study was undertaken for the most commonly performed gynecologic oncology procedure: total abdominal hysterectomy and oophorectomy with pelvic and para-aortic node sampling for endometrial cancer. Thirty consecutive women treated on the care path were compared with 29 matched controls accrued during the period of care-path planning and with 73 controls from the period preceding care-path planning. Patient satisfaction with care-path treatment was assessed by a survey sent 2 weeks after discharge.Results: Median length of hospital stay decreased significantly, from 6 days before care-path planning to 4 days after care-path implementation (P < .001). Median laboratory costs decreased by 74% (P < .001), medication costs by 35% (P < .001), room costs by 29% (P < .001), and total hospital costs by 20% (P < .002). Incremental improvements were observed during care-path planning. There were no readmissions for complications in the care-path group. According to the survey results, patient satisfaction with care was very high among care-path patients.Conclusions: A physician-driven outcomes-management program in an academic setting permits the delivery of high-quality care and supports outcomes research while decreasing costs. (C) 1997 by The American College of Obstetricians and Gynecologists.

PURPOSE:To evaluate the role of surgical debulking in patients with stage IV ovarian cancer.METHODS:We conducted a retrospective review of patients with advanced epithelial ovarian cancer treated at M. D. Anderson Cancer Center. Eligible patients included women with stage IV disease treated with platinum-based chemotherapy. Surgical debulking was considered optimal if the diameter of the largest residual tumor was 2 cm or less. Survival analysis and comparisons were performed using the Kaplan-Meier method and the log-rank test.RESULTS:One hundred eight women with stage IV ovarian cancer were identified. The extraperitoneal metastatic sites were the liver parenchyma in 16 patients, the pleura in 54 patients, a variety of other organs in 22, and two or more sites in the remaining 16. Median age of the patient population was 58 years (range 35-81 years). Surgery to reduce the primary tumor was performed in 100 patients. The procedures included salpingo-oophorectomy with or without hysterectomy in 94 patients, omentectomy in 90, small bowel resection in 4, large bowel resection in 23, and splenectomy in 2. At the completion of surgery, tumor reduction was considered optimal in 31 patients, suboptimal in 61, and undetermined in 8. The overall median survival for optimally debulked patients was 25 months compared to 15 months for suboptimally debulked patients (P < 0.02). The progression-free survival, on the other hand, was not statistically different between the two groups.CONCLUSION:Residual tumor seems to be an important prognostic factor in patients with stage IV ovarian cancer. Surgical debulking may play a significant role in the treatment of these patients.