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Biomedical subjects

J Curtin

Publications and source records attributed to J Curtin.

At least 55 records · Page 3Linked to original sources
PubMed1993

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.

Adult↗
PubMed1993

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.

Adult↗
PubMed1993

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.

Carboplatin↗
PubMed1993

Intraperitoneal carboplatin and etoposide for persistent epithelial ovarian cancer: analysis of results by prior sensitivity to platinum-based regimens.

Eighteen women with epithelial ovarian cancer and small-volume disease within the peritoneal cavity at reassessment laparotomy after initial treatment with platinum-based regimens received treatment with a combination of intraperitoneal (ip) carboplatin and etoposide administration. The dose of carboplatin was fixed at 200 mg/m2 whereas the dose of etoposide was escalated in cohorts of 4 patients from 50 to 75 and eventually to 100 mg/m2. Hematologic toxicities appeared to be related to decreased renal function, and, in the last cohort of 10 patients, with prior treatment with systemic carboplatin. Because of this shift in patient population, escalations ceased and ip cisplatin was partly substituted for ip carboplatin in 5 patients. The study opened July 1988 and closed on July 1991: 8 patients are alive, with 4 enjoying progression-free survival and no clinical evidence of disease 1 to 4 years after onset of treatment. One patient is alive with no clinical evidence of disease 3+ years after a late relapse was treated with systemic carboplatin. Three other patients are alive with evidence of disease, having experienced improvements with taxol and ip floxuridine. Analysis of this small experience by pretreatment characteristics suggests that patients who are platinum sensitive and not allowed to relapse, have normal baseline CA-125s, and undergo successful secondary cytoreductive surgery may benefit from platinum-based ip therapy.

Adult↗
PubMed1993

Diethyldithiocarbamate chemoprotection of carboplatin--induced hematological toxicity.

Carboplatin therapy has a more favorable toxicity profile than cisplatin and, given in appropriate doses, is equivalent in efficacy to cisplatin for suboptimal ovarian cancer. However myelosuppression frequently curtails therapy with carboplatin. Diethyldithiocarbamate (DDTC) is a thiol compound and heavy-metal-chelating agent that has been shown to protect against carboplatin-induced bone marrow suppression in animal models. This pilot study was undertaken to evaluate the ability of DDTC to ameliorate the degree and/or duration of myelosuppression from carboplatin chemotherapy in patients with relapsed ovarian cancer. Ten patients who had previously demonstrated a response to platinum-based chemotherapy, were treated with single-agent intravenous carboplatin 400 mg/m2 administered over 30-60 min every 4 weeks. Patients received their first cycle of carboplatin without DDTC, and their second cycle with DDTC. DDTC at 600 mg/m2 was infused over 3 h commencing 30 min prior to carboplatin and was well tolerated. Treatment with DDTC did not decrease the degree of leukopenia or thrombocytopenia associated with carboplatin chemotherapy, nor did it decrease the duration of myelosuppression. This clinical study demonstrates no evidence of a bone-marrow-protective effect for this dose and schedule of DDTC in patients receiving carboplatin chemotherapy.

Adenocarcinoma, Papillary↗
PubMed1993

Phase II trial of zeniplatin (CL 286,558), a new patinum compound, in patients with advanced ovarian cancer previously treated with organoplatinum-based therapy.

There is a critical need to find new chemotherapeutic agents that are active in platinum-refractory ovarian cancer. A phase II trial of zeniplatin (CL 286,558), a third-generation platinum compound, was conducted in 31 patients with advanced ovarian cancer to examine the safety and activity of the agent when used as a salvage treatment in individuals previously exposed to organoplatinum-based therapy. In general the drug was well tolerated, with moderate emesis and bone marrow suppression being observed in most patients. An unexpected side-effect was significant fever, of unknown etiology, which was noted in 16% of patients. Out of 20 patients, 2 (10%; 95% confidence intervals: 1%-32%) with clinically defined platinum-refractory disease achieved a partial response. Unfortunately, although we have defined definite but modest activity for zeniplatin in platinum-refractory ovarian cancer, further development of this drug has been discontinued because of the severe renal toxicity observed in other clinical trials of this cytotoxic agent.

Adult↗
PubMed1993

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.

Female↗
PubMed1992

Impact of laparotomy finding of significant intraabdominal adhesions on the surgically defined complete response rate to subsequent salvage intraperitoneal chemotherapy.

One possible explanation for the failure of the high concentrations of cytotoxic agents achieved following intraperitoneal (i.p.) drug delivery to produce a favorable response in patients with ovarian cancer is the inability of the drug-containing fluid to be adequately distributed throughout the peritoneal cavity, usually because of intraabdominal adhesion formation. To evaluate the influence of the severity of adhesions, observed at the time of laparotomy performed immediately preceding the initiation of i.p. therapy, on the ability to achieve a surgically defined complete response (S-CR), we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 salvage i.p. trials at the Memorial Sloan-Kettering Cancer Center. The S-CR rate in the 36 patients with limited adhesion formation observed upon entering the peritoneal cavity was 28%, compared to 35% in the 34 patients with extensive adhesions (P greater than 0.05). In 33 patients treated with a phase-2 cisplatin-based i.p. program, who had previously responded to systemic platinum, 47% (8/17) and 44% (7/16) of those with limited and extensive adhesions, respectively, achieved a S-CR (P greater than 0.05). We conclude that the presence of extensive adhesions observed within the peritoneal cavity at the time of a laparotomy performed immediately prior to the initiation of i.p. therapy does not have a negative impact on the potential to achieve an S-CR, assuming it is technically feasible to lyse all significant adhesions prior to the completion of the operative procedure.

Abdomen↗
PubMed1992

Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum-refractory ovarian cancer.

Eighteen previously treated patients with advanced ovarian cancer were entered into a phase 2 trial of chronic low-dose oral etoposide (50 mg/day for 20 days, repeated every 28 days) to determine the activity of this therapeutic strategy in organoplatinum-refractory disease. The treatment program was generally well tolerated, with mild neutropenia the most common side-effect encountered. One patient (6%; 95% confidence interval = 0-17%) achieved a partial response, which lasted for 11 months. Three additional patients (17%), who failed to meet the criteria of a partial response, demonstrated objective evidence of antineoplastic activity. Chronic low-dose oral etoposide administration is associated with definite, although modest, activity in platinum-refractory ovarian cancer.

Carboplatin↗
PubMed1992

Association between pretreatment CA-125 levels and surgically documented complete responses in patients with ovarian cancer treated with second-line intraperitoneal therapy.

Approximately 20%-40% of patients with small-volume residual ovarian cancer, following systemically administered platinum-based chemotherapy, will respond to a second-line intraperitoneal treatment regimen. In an effort to improve the selection criteria for patients being considered for this regional therapeutic approach, we retrospectively evaluated the influence of pretreatment CA-125 levels on the ability of a group of 70 patients with small-volume residual ovarian cancer (no tumor mass greater than 1 cm in diameter) to achieve a surgically defined complete response (S-CR) following treatment on one of three phase-2 intraperitoneal chemotherapy trials conducted at the Memorial Sloan-Kettering Cancer Center. Overall, 18/46 (39%) patients with normal pretreatment CA-125 levels (less than or equal to units/ml) achieved a S-CR, compared to only 4/24 patients (17%) with an elevated pretreatment value (chi 2 = 3.7, P greater than 0.5). Despite the lower S-CR rate in patients with elevated CA-125 levels, the duration of response and survival were similar in the two patient populations achieving a S-CR. Thus, we conclude that an elevated pretreatment CA-125 level in a patient with small-volume residual ovarian cancer should not be used by itself to disqualify an individual from consideration for a second-line intraperitoneal treatment regimen, although the finding suggests a reduced likelihood of achieving a S-CR with this therapeutic approach.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Salvage intraperitoneal therapy of small-volume residual ovarian cancer: impact of pretreatment finding of peritoneal carcinomatosis on the surgical complete response rate.

Second-line intraperitoneal (i.p.) therapy has been demonstrated to result in surgically defined complete responses (S-CR) in 25%-40% of patients with small-volume residual ovarian cancer (microscopic disease or largest tumor mass less than 1 cm in diameter). To evaluate the influence of the surgical finding of diffuse peritoneal carcinomatosis on the S-CR rate to salvage i.p. therapy in this patient population, we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 second-line i.p. trials at the Memorial Sloan-Kettering Cancer Center. Of the 11 patients with diffuse carcinomatosis, none achieved a S-CR compared to a S-CR rate of 37% (22/59) in patients without this surgical finding (chi 2 = 6.0; P less than 0.025). However, of the 7 patients with diffuse carcinomatosis treated on a cisplatin-based i.p. program, the only 2 who had previously responded to systemic platinum also experienced a response (partial) to the i.p. cisplatin regimen. In conclusion, while the surgical finding of diffuse peritoneal carcinomatosis indicates a poor prognosis in patients with small-volume residual ovarian cancer for response to i.p. chemotherapy, patients in this clinical setting with prior evidence of platinum sensitivity may experience some benefit from an i.p. cisplatin-based treatment strategy.

Cisplatin↗
PubMed1992

Phase 2 trial of intraperitoneal carboplatin and etoposide as salvage treatment of advanced epithelial ovarian cancer.

To evaluate the efficacy of intraperitoneal (IP) carboplatin-based therapy as salvage treatment of ovarian cancer, 46 patients with persistent or recurrent ovarian cancer following initial systemic chemotherapy were treated with a regimen of carboplatin (200-300 mg/m2) and etoposide (100 mg/m2) administered on a monthly schedule. A maximum of six courses of therapy was delivered, followed by a response laparotomy. The treatment program was well tolerated, except for bone marrow suppression, with one-quarter of patients developing platelet count depressions to < or = 50,000/mm3, and one-third experiencing hemoglobin levels of < or = 8 g/dl during treatment. Twelve (38%) of 32 patients evaluable for efficacy of the treatment program achieved a surgically documented response, including 8 (25%) complete responses. Of 25 patients whose largest tumor mass at the initiation of therapy measured < or = 0.5 cm, 11 (44%) responded, including 8 (32%) complete responses. We conclude that the IP administration of carboplatin can result in surgically documented responses when used in the salvage setting in patients with advanced ovarian cancer. The relative efficacy of carboplatin versus cisplatin when administered by the IP route to patients with ovarian cancer previously treated with platinum-based systemic therapy remains to be defined.

Adult↗
PubMed1992

Intraperitoneal therapy for ovarian cancer: analysis of fluid distribution by computerized tomography.

Nineteen patients with ovarian cancer and minimal residual or persistent disease who were treated with cisplatin or carboplatin-based intraperitoneal (IP) regimens had distribution studies of IP contrast and computerized tomography prior to and during treatment. The distribution pattern was assessed retrospectively and scored for the presence of contrast in each of eight regions: the under surface of right and left diaphragms, the right and left paracolic gutters, the lesser omental sac, the intramesenteric region and the true and false pelvis. Assigning a point to each region with adequate distribution, we classified 10 patients to an excellent pattern (greater than or equal to 7 of 8 regions), 6 to a good pattern (5 to less than 7 regions), and 3 to an inadequate distribution pattern (less than 5 regions). Serial studies were performed in 8 patients after more than 4 cycles of IP therapy. In these patients, all of whom were tolerating treatment without progression, the distribution remained virtually unchanged for those with excellent distribution. One of three with good distribution manifested inadequate distribution on repeat study, and one of two with inadequate distribution improved to show a good pattern. In this small study there was no correlation of distribution patterns with plasma CA-125 at onset of IP treatment and prior surgical procedures or placement of the catheter tip. However, three patients with unsatisfactory patterns had procedures consisting of catheter placement only rather than formal reassessment laparotomies for ovarian cancer. Since satisfactory IP distribution may be required for obtaining a therapeutic advantage from IP therapy, methods for its assessment must be developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer.

PURPOSE: To evaluate the impact on survival of the attainment of surgically defined favorable responses (S-R) to salvage intraperitoneal (IP) chemotherapy after initial systemic cytotoxic drug delivery. PATIENTS AND METHODS: We examined the survival of patients who were treated on one of three phase II IP trials that were conducted at the Memorial Sloan-Kettering Cancer Center. A total of 58 patients whose largest residual tumor masses measured less than or equal to 0.5 cm in maximum diameter at the initiation of this salvage therapy were assessable for response, 28 of whom (48%) demonstrated a S-R, which included 19 (33%) who achieved a surgically defined complete response (S-CR). RESULTS: With a median follow-up of 43+ months (range, 33+ to 58+ months) from the initiation of IP therapy, 12 of 19 (63%) have recurred. The median duration of S-CR for the 10 patients with microscopic residual disease was 32 months compared with 15 months for the nine patients with macroscopic residual disease (largest tumor mass less than or equal to 0.5 cm; P greater than .1). For patients with microscopic residual disease who experienced a S-CR (n = 10) after salvage IP therapy, the median overall survival from the initiation of therapy has not been reached, but will exceed 4 years compared with a 25-month median survival for the nonresponding patients (n = 13; P = .004). The median survival for the 18 patients with small-volume macroscopic disease who responded to therapy was 40 months compared with 19 months for the nonresponders (P = .009). CONCLUSION: Although the results of this evaluation are encouraging and suggest that the attainment of a S-R, particularly a S-CR, after IP chemotherapy may result in a clinically meaningful favorable impact on survival, a randomized controlled trial will be required to address definitively this important issue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.

PURPOSE: To evaluate the safety and pharmacology of the intraperitoneal (IP) administration of the antineoplastic agent taxol. PATIENTS AND METHODS: Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were no intrapatient dose escalations. RESULTS: The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. CONCLUSION: Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.

Alkaloids↗
PubMed1992

Lunate Silastic arthroplasty in Kienbock's disease.

The use of Silastic lunate replacement for Kienbock's disease has many advocates. We reviewed the long-term results of eight patients who had this procedure performed. Although good short-term results were obtained, this was not maintained and only two patients were regarded as satisfactory at an average follow-up time of 44 months. Evidence of synovitis was apparent in seven cases. It is now our view that if surgical intervention is necessary for this condition, the best surgical option is probably a scapho-trapezio-trapezoid fusion.

Adolescent↗