Identification of risk factors for requiring transfusion during front-line chemotherapy for ovarian cancer.

OBJECTIVE: Anemia requiring red blood cell (RBC) transfusion is common in ovarian cancer (OC) patients receiving post-debulking surgery chemotherapy. Erythropoietin use has been shown to decrease transfusion requirements in patients receiving chemotherapy. We sought to identify pretreatment risk factors that could identify patients at increased risk for requiring RBC transfusion during first-line treatment for ovarian cancer. METHODS: One hundred seventy-five consecutive patients who received chemotherapy with either carboplatin-paclitaxel or cisplatin-paclitaxel following debulking surgery for epithelial OC from 1993 to 1996 were identified. No patient received erythropoietin. Patient characteristics recorded included: age, stage, prechemotherapy hemoglobin, nadir hemoglobin, number of cycles and doses of chemotherapy received. The outcome was requiring RBC transfusion. Independent predictors of requiring RBC transfusion were identified using multivariate analyses. RESULTS: Median age of the cohort was 62 years (range, 28-86). Seventy-one and four-tenths percent had FIGO stage III/IV disease. Median prechemotherapy hemoglobin was 11 g/dL (range, 7.1-15.4); median nadir hemoglobin was 9.3 g/dL (range, 6.6-11.1). One hundred nineteen (66%) patients received cisplatin-paclitaxel, and 61 (34%) received carboplatin-paclitaxel. Of 175 patients, 31 (18%, 95% CI = 12-23%) required RBC transfusion. Independent risk factors for RBC transfusion were prechemotherapy hemoglobin <10 g/dL (P < 0.01, odds ratio = 3.78, 95% CI = 1.52-9.44) and carboplatin-paclitaxel versus cisplatin-paclitaxel treatment (P = 0.01, odds ratio = 3.14, 95% CI = 1.27-7.76). Of 175 patients, 40 (22.8%) had a prechemotherapy hemoglobin <10 g/dL. Fifty percent of patients with prechemotherapy hemoglobin <10 g/dL who received carboplatin-paclitaxel required RBC transfusion, compared with 7.7% of patients with hemoglobin >10 g/dL who received cisplatin-paclitaxel. CONCLUSION: Ovarian cancer patients frequently require RBC transfusion during postdebulking platinum-paclitaxel chemotherapy. Patients with prechemotherapy hemoglobin <10 g/dL and those receiving carboplatin-paclitaxel are at increased risk of requiring RBC transfusion. Early initiation of erythropoietin use in such patients may reduce transfusion needs.

Complications associated with intraperitoneal chemotherapy catheters.

PURPOSE: The goal of this work was to determine the complication rate and any predisposing risk factors associated with subcutaneous intraperitoneal (ip) catheters used in the treatment of patients with advanced ovarian cancer. METHODS: We retrospectively reviewed the charts of 301 patients who had a subcutaneous Bardport catheter placed for administration of ip chemotherapy at Memorial Sloan--Kettering Cancer Center (MSKCC) from December 1989 to May 1997. RESULTS: Thirty (10%) patients were identified as having catheter-related complications, with 19 (6.3%) experiencing inflow obstruction and 11 (3.6%) experiencing infection. Only 21 of 301 (7%) required cessation of chemotherapy prior to its expected completion, with 14 (4.6%) occurring in the malfunction group and 7 (2.3%) in the infection group. Three hundred thirteen patients received an ip catheter; however, 12 patients who received their ip chemotherapy elsewhere were excluded when determining the complication rate. Overall, 218 of 313 (69.6%) catheters were placed at the time of laparotomy, 61 of 313 (19.5%) catheters were placed at the time of laparoscopy, and 34 of 313 (10.9%) were placed as a separate procedure. In the malfunction group, 18 of 19 (94.7%) patients had their catheters placed at the time of laparotomy, none were placed at the time of laparoscopy, and 1 of 19 (5.3%) was placed as a separate procedure. In the infection group, 8 of 11 (72.7%) catheters were placed at laparotomy, 2 of 11 (18.3%) were placed at the time of laparoscopy, and 1 of 11 (9.0%) was placed as a separate procedure. Complications occurred in 3 of 54 (5.5%) patients who received platinum alone, 11 of 134 (8.2%) who received platinum in combination, 2 of 43 (4.7%) who received paclitaxel alone, 13 of 61 (21.3%) who received mitoxantrone alone or in combination, and 1 of 9 (11.1%) who received other regimens. CONCLUSION: Subcutaneous ip catheters are associated with a lower rate of catheter-related complications than previously reported, perhaps due in part to both avoiding insertion of ip catheters at the time of bowel surgery and placing ip catheters at the time of laparoscopy.

Effect of adjuvant tamoxifen on the endometrium in women with breast cancer: a prospective study using office endometrial biopsy.

PURPOSE: To determine the frequency of developing abnormal pathologic changes in the endometria of tamoxifen-treated women. To characterize the type of pathologic changes involved. PATIENTS AND METHODS: Between October 1991 and September 1998, 159 patients initiating tamoxifen therapy for breast cancer confined to the breast and axillary lymph nodes were entered in a prospective study. In this study, office endometrial biopsies (EMBs) were obtained during the initiation of tamoxifen and at 6-month intervals for a 2-year period. Three subsequent annual EMBs were recorded for each patient, amounting to a 5-year surveillance. RESULTS: One hundred fifty-nine patients with a median age of 50 years were entered onto study. Patients were assessable if EMBs were performed at least 1 year after the initiation of tamoxifen treatment. Nine patients (5. 7%) were considered protocol violations. The remaining 111 assessable patients underwent a total of 635 EMBs (mean, 5.8 EMBs), with a median surveillance time of 36 months. Eighty-two (12.9%) of the 635 biopsies revealed tissue insufficient for diagnosis. Fourteen patients (12.6%) underwent dilation and curettage (D&C) for an abnormal EMB, persistent bleeding, or for evaluation of adnexal masses at the time of laparoscopy. Findings at D&C included complex hyperplasia (n = 1), abnormal histiocytes (n = 1), simple hyperplasia (n = 2), polyps (n = 4), endocervical polyp (n = 1), and decidualization (n = 2). Three D&Cs were negative. Three patients have undergone hysterectomy. CONCLUSION: EMB was used to monitor the endometrium in the majority (95%) of breast cancer patients on tamoxifen in this trial, but the utility of routine EMB for screening in tamoxifen-treated women seems limited.

Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.

CONTEXT: Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival. OBJECTIVE: To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. DESIGN AND SETTING: Retrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PATIENTS: The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison. MAIN OUTCOME MEASURES: Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advanced-stage (II and IV) cases. RESULTS: Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1- vs BRCA2-linked patients (54 vs 62 years; P=.04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (P<.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P=.03). CONCLUSIONS: Although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

Patient guide to peripheral neuropathy.

PURPOSE/OBJECTIVES: To describe a booklet used to educate patients who experience peripheral neuropathy secondary to neurotoxic chemotherapy treatment. DATA SOURCES: Journal articles, neurologic physical assessment, symptom management books. DATA SYNTHESIS: The booklet defines peripheral neuropathy, the types of nerves most often affected, common causes and symptoms, and management strategies with an emphasis on safety issues. It contains a list of referral sources for additional management information and a glossary of terms related to peripheral neuropathy. CONCLUSIONS: The booklet is useful for patients in their daily management of peripheral neuropathy that has occurred as a side effect of neurotoxic chemotherapy treatment. IMPLICATIONS FOR NURSING PRACTICE: Nurses can use this information to educate patients and their caregivers about peripheral neuropathy. The booklet offers strategies to manage this side effect and maintain a safe home environment and workplace. It also offers sources of information and referrals that may benefit patients with peripheral neuropathy.

A phase II trial of intraperitoneal cisplatin and etoposide as consolidation therapy in patients with Stage II-IV epithelial ovarian cancer following negative surgical assessment.

PURPOSE: To determine the efficacy of three courses of intraperitoneal (i.p.) cisplatin (CDDP) and etoposide (VP-16) as consolidation therapy following pathologically negative second-look surgical reassessment for Stage IIC-IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Between September 1988 and April 1996, 40 patients were treated with three cycles of i.p. CDDP (100 mg/m2)/VP-16 (200 mg/m2) as consolidation therapy. Survival was compared to that of a group of 46 contemporaneous patients undergoing observation only. RESULTS: Median age of the 36 eligible patients was 52 years (range 30-70 years). Stage distribution was II (3), III (31), and IV (2); histologic grade was 1 (2), 2 (7), 3 (25), and not recorded (2); and residual disease at completion of initial surgery was none/microscopic in 13/36 (36%) patients. Median age of the 46 patients who did not receive consolidation was 52 years (range, 27-80 years); stage distribution was II (18), III (26), and IV (2); histologic grade was 1 (5), 2 (12), 3 (28), and not recorded (1). With a median follow-up of 36 months in both groups, 14/36 (39%) of the protocol group have recurred compared with 25/46 (54%) of those undergoing observation alone. Median disease-free survival (DFS) for the observed patients is 28.5 months and has not been reached in the consolidation group. Disease-free survival distribution between the two groups was compared using the log-rank test and was found to be significant (P = 0.03). Multivariate analysis revealed that the only significant predictor of improved DFS was protocol treatment (P < 0.01). CONCLUSION: Intraperitoneal consolidation with CDDP/VP-16 following negative second-look reassessment in patients with advanced EOC resulted in a significant increase in DFS compared to nonprotocol patients treated concurrently who underwent observation alone.

Palliative benefit of external-beam radiation in the management of platinum refractory epithelial ovarian carcinoma.

In vitro studies and clinical experience have suggested that patients with platinum-refractory epithelial ovarian carcinoma exhibit cross-resistance to radiation. Salvage with radiation in these patients is rare. However, radiation is often utilized to palliate symptoms caused by these chemotherapy-resistant tumors. Forty-seven patients with platinum-refractory epithelial ovarian carcinoma were referred for palliative radiation and 33 (70%) were evaluable for response. One to four regimens of platinum-based chemotherapy (median 2.7) were given to each patient prior to radiation therapy. Of the 33 evaluable patients, 23 (69.7%) had a complete resolution of symptoms after radiation, 8 (24%) had a partial resolution, and 2 were unassessable because of unrelated medical complications. The median duration of response was 11 months (range 1-86) and closely approximated their survival. Thirteen of 33 patients (39%) obtained relief of symptoms for greater than 12 months, with 10 of 33 (30%) having symptoms controlled for 6 to 12 months. In only 10 patients (30%) was the duration of palliation less than or equal to 6 months. Four patients required reirradiation to the same area for recurrence of their symptom. External-beam radiation therapy can provide effective and durable palliation of symptoms in platinum-refractory epithelial ovarian carcinoma patients.

Phase II study of "dose-dense" high-dose chemotherapy treatment with peripheral-blood progenitor-cell support as primary treatment for patients with advanced ovarian cancer.

PURPOSE: We performed a pilot phase II study to evaluate the potential for delivery of rapidly sequenced high-dose chemotherapy treatments rescued with autologous peripheral-blood progenitor cells (PBP) in patients with previously untreated, advanced ovarian cancer. PATIENTS AND METHODS: A single cycle of mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan (MEL), each rescued by PBP. We then analyzed the outcome for a total of 56 consecutive patients treated with high-dose chemotherapy as part of this program. RESULTS: In the phase II pilot, 21 patients were enrolled. There were no treatment-related deaths through 98 high-dose treatments, although 34 treatments were complicated by hospitalization, primarily for neutropenic fever. Seventy-six percent of patients experienced grade 3 to 4 gastrointestinal toxicity and 62% experienced grade 2 to 3 neuropathy. Five of 15 (33%) patients who underwent second-look surgery attained a pathologic complete response. In the overall analysis, 56 patients were reviewed. Forty-four patients were assessable for response by second-look surgery or clinical progression. Fifteen of 44 patients achieved a pathologic complete response (34%). The pathologic complete response rate in optimal-disease patients was 12 of 22 (55%), while only three of 22 (13%) suboptimal stage III and IV patients achieved a pathologic complete response. CONCLUSION: The Gynecologic Oncology Group has initiated a pilot phase II trial of this approach in patients with optimally debulked stage III ovarian cancer. There is no evidence to support the use of this or other aggressive regimens outside of a clinical trial.

High-intensity intravenous cyclophosphamide and cisplatin, interim surgical debulking, and intraperitoneal cisplatin in advanced ovarian carcinoma: a pilot trial with ten-year follow-up.

PURPOSE: This trial was undertaken to study the effect of intensified intravenous cyclophosphamide/cisplatin and interim surgical debulking, followed by intraperitoneal cisplatin on surgically defined complete remission rate and survival in advanced ovarian cancer. PATIENTS AND METHODS: Forty patients with stage IIB through IV ovarian cancer were entered and 36 were evaluable for response and survival and approximately 10 years. Following a first laparotomy for diagnosis and debulking, the patients received two cycles, spaced 28 days apart, of intravenous cisplatin 30-40 mg/m2/day with hypertonic saline for 4 to 5 days and cyclophosphamide 200 mg/m2/day for 5 days. A second laparotomy was done to further debulk remaining cancer and to place an intraperitoneal catheter. Four cycles of intraperitoneal cisplatin at 50 or 100 mg/m2 were administered 21 days apart and followed by a third laparotomy to define response and plan any further therapy. RESULTS: The surgically confirmed complete response rate was 47% and median survival is 68.3 months for this group. Ten of the 17 patients (58.8%) relapsed following complete response at a median of 19.5 months (range, 5-98). Both aggressive chemotherapy and surgery seemed to play a role in inducing this high complete response rate. Traditional prognostic factors, including stage and diameter of largest residual disease, had little apparent effect on likelihood of complete response or survival, whereas tumor grade had a more significant effect on survival. Nadir fever was experienced by 33% of patients but peripheral neuropathy was dose limiting. CONCLUSION: In the context of recent data failing to support any clinical benefit to modest increases in dose escalations of cisplatin or carboplatin, in this trial the high complete response rate suggests that the multimodality approach (i.e., interval surgical debulking and intraperitoneal cisplatin) is worthy of further study. The high relapse rate among complete responders and the unacceptable neurotoxicity also suggest that modifications could improve the results. The use of newer agents and further intensification (substituting carboplatin for cisplatin and the use of paclitaxel) with stem cell support are two examples.

The impact of diabetes mellitus on the toxicity of therapy for advanced ovarian cancer.

A retrospective review was undertaken to obtain more precise information about neurotoxicity, nephrotoxicity, and the effects of dexamethasone on the frequency and severity of hyperglycemia in diabetic patients with epithelial ovarian cancer treated with paclitaxel and/or cisplatin. Thirty-three patients were identified from 1254 patients over a 10-year period. In the cisplatin-treated patients, 21 of 24 (67%) had progression of neurological symptoms, three experienced grade 3 sensory neuropathy, and two had ototoxicity. Four patients had evidence of mild nephrotoxicity and two required a 50% dose reduction. In the group of patients treated with paclitaxel, 9 of the 18 (50%) had progression of symptoms, 2 to grade 3, and 2 had ototoxicity. No discontinuation of therapy due to neuropathy was required and no patient had evidence of drug-induced autonomic nervous system dysfunction. Hyperglycemia was frequently exacerbated, and 5 patients required treatment change, but no patient was hospitalized in relation to this. Our results indicate that the paclitaxel/cisplatin combination regimen or paclitaxel alone could be safely administered in diabetic patients at standard doses, with concurrent glucose and creatinine monitoring, as well as history of neurological symptoms and physical examination.

Adjuvant chemotherapy versus chemotherapy plus pelvic irradiation for high-risk cervical cancer patients after radical hysterectomy and pelvic lymphadenectomy (RH-PLND): a randomized phase III trial.

OBJECTIVE: To compare the clinical efficacy of adjuvant chemotherapy a lone vs chemotherapy plus whole pelvic radiation therapy (RT) on recurrence rates, patterns of recurrence, and survival of patients post-RH-PLND for cervical cancer at high risk for recurrence. METHODS: Prospective multicenter randomized Phase III trial. Patients with Stage IB-IIA cervical cancer undergoing RH-PLND were eligible. Risk factors include deep cervical invasion, tumor > or = 4 cm, parametrial involvement, nonsquamous histology, and/or pelvic lymph node metastasis. Chemotherapy consisted of cisplatin and bleomycin, alone or in combination with whole pelvic RT. Survival was determined by Kaplan-Meier estimate. RESULTS: Eighty-nine patients were entered from 1987 to 1994. Seventy-five patients had a Stage IB cancer and 14 patients had Stage IIA. Twenty-five patients had > or = 3 risk factors. Forty-four patients received chemotherapy alone vs 45 patients treated with chemotherapy and RT. Nineteen patients had recurrences and 16 patients have died. Nine of 44 (20%) patients receiving chemo alone recurred compared to 10/45 (22%) patients receiving chemo and RT (P=ns). Patterns of recurrence were statistically similar between the two treatment arms, even among the subgroup of patients with > or = 3 risk factors. Both regimens were well tolerated. CONCLUSION: CT + RT did not prove a superior adjuvant therapy for patients at high risk of recurrence after RH-PLND for early cervical cancer in this limited trial. Recurrence rates and patterns of recurrences (local, regional, or distant) were not influenced by the addition of RT.

Follow-up of Memorial Sloan-Kettering Cancer Center patients treated on National Cancer Institute Treatment Referral Center protocol 9103: paclitaxel in refractory ovarian cancer.

PURPOSE: To examine the short-term and long-term results of paclitaxel therapy in patients with advanced heavily pretreated, cisplatin-refractory ovarian cancer. PATIENTS AND METHODS: The results of treatment for patients entered onto National Cancer Institute (NCI) Treatment Referral Center protocol 9103 at the Memorial Sloan-Kettering Cancer Center (MSKCC) were reviewed to evaluate toxicity, efficacy, and survival. RESULTS: Of 46 individuals with measurable disease treated on the protocol at MSKCC, the objective response rate was only 4%. However, the 2- and 3-year survival rates for all 103 patients (including both measurable and nonmeasurable populations) entered onto this study at MSKCC were 18% and 11%, respectively. Twenty-one percent of patients received > or = six courses of paclitaxel, which suggests treatment-related stabilization of disease may have had a greater impact on the natural history of the malignancy than indicated by the objective response rate. CONCLUSION: This experience supports the hypothesis that a more prolonged delivery of paclitaxel (ie, > six courses), a cell-cycle-specific cytotoxic agent with limited or no cumulative toxicity, may result in an improved therapeutic outcome in ovarian cancer. This concept will need to be tested in a randomized phase 3 clinical trial.

Arterial, peritoneal, and intraventricular access devices.

OBJECTIVE: To provide an overview of access devices used to treat cancers through the arterial, peritoneal, and intraventricular body systems. CONCLUSIONS: Short-term and long-term devices have been developed over the last 35 years for cancer treatment. Although less amenable to standard methods of therapy, the various access devices available to access the arterial, peritoneal, and intraventricular systems have provided a safe and reliable means for drug therapy. Access devices assist in delivering high concentrations of drugs directly to the center of the tumor. Complications and toxicities are inherent with these devices from the drug therapy as well as the device. Nursing assessment can provide early identification of potential problems and implementation of appropriate interventions. IMPLICATIONS FOR NURSING PRACTICE: As the availability of these devices increases, so must the nurse's knowledge base to provide optimal safe care. Oncology nurses are challenged to know the differences between the devices, the device of choice for the individual patient, insertion procedures, and maintenance protocols.

Evidence supporting the superiority of intraperitoneal cisplatin compared to intraperitoneal carboplatin for salvage therapy of small-volume residual ovarian cancer.

PURPOSE: To examine the relative efficacy of cisplatin-based intraperitoneal (IP) therapy versus carboplatin-based IP therapy as salvage treatment of small-volume residual ovarian cancer. PATIENTS AND METHODS: We retrospectively examined the surgically defined response rates of patients with ovarian cancer treated at the Memorial Sloan-Kettering Cancer Center on four organoplatinum-based salvage IP trials (cisplatin/etoposide, cisplatin/cytarabine, carboplatin/etoposide, carboplatin/etoposide + recombinant human erythropoietin). Additional criteria for inclusion in this analysis were: (a) small-volume residual disease (microscopic disease only or largest residual tumor mass < or = 0.5 cm) when IP therapy was initiated; (b) prior response to organoplatinum-based systemic therapy; (c) laparotomy evaluation for response to the IP salvage program. RESULTS: The surgically documented complete response rate for patients with microscopic disease treated with cisplatin-based or carboplatin-based therapy was 46% (6/13) versus 38% (6/16), respectively (P > 0.25). In contrast, the surgically documented overall and complete response rates for patients with small-volume macroscopic disease treated with cisplatin or carboplatin were 71% (12/17) versus 32% (6/19) (P < 0.05, chi 2 test with Yates' correction), and 41% (6/17) versus 11% (2/19) (p < 0.1), respectively. CONCLUSION: In agreement with experimental data demonstrating that the concentration of platinum within tumor is higher following equimolar doses of cisplatin, compared to carboplatin, we have observed, in this retrospective analysis, a higher surgically documented response rate for patients with small-volume residual macroscopic ovarian cancer receiving salvage cisplatin-based IP therapy. While a randomized trial will be required to definitively address the question of the relative effectiveness of the two commercially available organoplatinum agents for IP treatment of ovarian cancer, our data suggest that cisplatin is the superior agent for regional therapy in this disease.

Mitomycin-C plus a 3-day continuous intravenous infusion of 5-fluorouracil: an inactive salvage regimen for platinum-resistant ovarian carcinoma.

In a Phase II trial, patients with refractory ovarian cancer were given 10 mg/m2 mitomycin-C i.v. every 8 weeks and 1000 mg/m2/day 5-fluorouracil for 3 consecutive days by continuous intravenous infusion repeated every 4 weeks. Sixteen heavily pretreated patients with platinum-resistant disease were treated and no major responses were observed. Only 2 patients required subsequent dose reduction for myelotoxicity. No sign of gastrointestinal toxicity was seen. This regimen is inactive as salvage treatment for refractory ovarian cancer.

Relationship between saliva and serum CA 125 in women with and without epithelial ovarian cancer.

OBJECTIVE: To determine the distribution of saliva CA 125 levels in women with and without ovarian cancer, and to determine whether there is a correlation between saliva and serum CA 125 levels in either group. METHODS: CA 125 levels were measured by immunoradiometric assay in the serum and saliva of 50 women with epithelial ovarian cancer known to have elevated serum CA 125 levels (above 35 U/mL) and in 50 women seen for benign gynecologic conditions. RESULTS: Serum and saliva CA 125 values followed a log-normal distribution in both groups. The medians for serum and saliva CA 125 levels in cancer patients were 578 and 1379 U/mL, respectively. In the benign group, the median CA 125 value was 11 U/mL in serum and 994 U/mL in saliva. The correlation between saliva and serum CA 125 levels was not statistically significant in either the cancer (r = 0.003) or the benign group (r = 0.025). CONCLUSION: There is no relationship between saliva and serum CA 125 levels in women with either epithelial ovarian cancer or benign gynecologic conditions.

The use of recombinant human erythropoietin to prevent carboplatin-induced anemia.

Anemia is a frequent and potentially serious toxicity associated with the use of carboplatin, particularly when this agent is administered in the salvage setting. In an effort to evaluate a possible role for human erythropoietin (rh-E) in preventing or minimizing carboplatin-induced anemia we analyzed the impact of the agent on anemia and transfusion requirements of women with ovarian cancer who were treated on one of two nonrandomized trials employing identical second-line carboplatin-based intraperitoneal regimens, with the only difference in the regimens being the addition of rh-E (Study 1, without rh-E; Study 2, with rh-E). There was a statistically significant difference in the incidence of documented nadir hemoglobin levels of < 9 g/dl (Study 1, 60%; Study 2, 13%; P < 0.005) and < 8 g/dl (Study 1, 33%; Study 3, 6%; P < 0.05). We also observed a threefold reduction in transfusion requirements with the use of rh-E (Study 1, 23%; Study 2, 6%), but this difference was not statistically significant with the limited sample size evaluated. In this nonrandomized comparison of two identical chemotherapy programs we have demonstrated that rh-E significantly reduced the incidence and severity of anemia associated with carboplatin-based chemotherapy. A randomized trial examining the potential impact of rh-E on carboplatin-induced anemia and transfusion requirements is warranted.

Salvage intraperitoneal mitoxantrone therapy of ovarian cancer: influence of increasing the volume of treatment.

Despite the demonstrated activity of intraperitoneal mitoxantrone in patients with small volume-platinum-refractory ovarian cancer, previous reports have revealed that many patients fail to achieve adequate distribution of the cytotoxic drug throughout the peritoneal cavity when delivered in a "standard" 2-liter treatment volume. In an effort to improve the distribution and therapeutic efficacy of intraperitoneal mitoxantrone, 22 patients with platinum-refractory ovarian cancer were treated with the drug at a dose of 10 mg/m2 given in 2 liters of normal saline followed by an additional 1-2 liters every 2 weeks for eight cycles. The surgically defined complete response rate in 17 patients evaluable for response with platinum-refractory ovarian cancer was 24%, with an overall response rate of 29%. Of 18 in which the influence of treatment volume could be examined (4 patients developed catheter failure), 12 (67%) were able to tolerate a 4-liter treatment volume for > 80% of courses, with a total of 15 patients (83%) receiving treatment with a minimum of a 3-liter treatment volume. We conclude that it is possible to safely increase the intraperitoneal treatment volume to 3-4 liters in most patients undergoing this therapeutic strategy. While the impact on therapeutic efficacy of expanding the volume employed for cytotoxic drug delivery remains to be defined, in theory this approach may optimize the opportunity for agents achieving high-intraperitoneal concentrations to produce their maximal cytotoxic effect.

Impact of age on survival of patients with ovarian cancer.

In an effort to determine if there are significant differences in outcome between elderly (> or = 65 years of age) and younger (< 65 years of age) women with epithelial ovarian cancer we examined the survival of patients with this malignancy who underwent their initial surgical evaluation at the Memorial Sloan-Kettering Cancer Center from January 1987-January 1991. The actuarial median overall survival for the 98 younger patients has not been reached but will exceed 4 years, compared to a median survival of 24 months for the 48 elderly patients (P < 0.0001). For individuals with advanced (stages 3-4) disease, excluding patients with tumors of low malignant potential, the median survival for the younger patient population has also not been reached and will exceed 4 years, compared to 21 months for the older population (P < 0.0001). Even in the limited number of patients with local/regional (stages 1-2) ovarian cancer, there was a statistically significant superior survival for the younger group of patients (P < 0.02). With a single exception, all deaths were believed to be due principally to disease progression, rather than to an unrelated comorbid medical event. We conclude that elderly patients with ovarian cancer experience a significantly inferior survival than younger individuals with this malignancy. Evaluation of larger populations will be required to confirm the results of this analysis and to probe for explanations for the striking survival differences we have observed.

Intraperitoneal administration of Taxol in the management of ovarian cancer.

The safety and pharmacology of the intraperitoneal administration of Taxol was evaluated by treatment of 25 patients (24 with ovarian cancer) on a phase I dose-escalation trial. The drug was delivered in 2 L of normal saline every 3 to 4 weeks, with a starting dose of 25 mg/m2. The dose-limiting toxicity was abdominal pain at Taxol doses greater than 125 mg/m2. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to Taxol, compared to the systemic compartment, was demonstrated following intraperitoneal delivery. In addition, high levels of Taxol persisted within the cavity for more than 48 hours following a single treatment. Despite the major pharmacokinetic advantage for peritoneal cavity exposure, significant concentrations of Taxol were demonstrated within the systemic compartment after intraperitoneal treatment. Several patients exhibited clinical and laboratory evidence of an antitumor response. Further exploration of a possible role for the intraperitoneal administration of Taxol in the management of ovarian cancer appears indicated.