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S Rubin

Publications and source records attributed to S Rubin.

At least 73 records · Page 4Linked to original sources
PubMed1993

Intraperitoneal chemotherapy in the management of ovarian cancer.

During the past decade, intraperitoneal therapy of ovarian cancer has evolved from a pharmacologic model into an established treatment technique for women with this malignancy. Approximately 40% of patients with small-volume residual ovarian cancer (microscopic disease or macroscopic tumor, < or = 0.5 cm in maximum tumor diameter), after an objective response to initial organoplatinum-based systemic chemotherapy, may have a surgically documented complete response to platinum-based intraperitoneal chemotherapy. Patients who have not responded to systemic platinum administration rarely will respond to the drug given intraperitoneally, despite the presence of only small-volume residual disease when this regional treatment strategy is used. Other agents with antineoplastic activity after intraperitoneal administration in women with ovarian cancer include mitoxantrone, taxol, alpha-interferon and gamma-interferon, and interleukin-2. Although intraperitoneal therapy currently is being examined as a component of the initial chemotherapeutic program for patients with ovarian cancer, a precise role for regional drug delivery in this clinical setting remains to be defined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Epithelial ovarian cancer in the elderly. The Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: There is evidence of differences between older (> or = 65 years of age) and younger (< 65 years of age) women with ovarian cancer. METHODS: To evaluate differences in the care of older versus younger patients with ovarian cancer, a retrospective review was conducted of the records of 146 patients who had their initial surgery for ovarian cancer at the Memorial Sloan-Kettering Cancer Center from January 1987-January 1991. RESULTS: There was a significant difference in stage at presentation between the older (48 patients) and younger (98 patients) populations (Stage I/II: older 10%; younger 25%; P < 0.05). Although there was no statistically significant difference in the distributions of patients according to tumor grade between the two groups, 10% of the younger patients had ovarian cancer of low malignant potential, compared to only 2% of older patients (P < 0.1). Forty-six percent of the younger patients entered an intensive initial chemotherapy trial compared to only 17% of the older patients (P < 0.001), principally due to comorbid medical conditions (e.g., heart disease). Finally, whereas the relative number of younger to older patients with ovarian cancer undergoing initial surgery at this institution was 2:1, the relative number of totally new patients to the service (including referral for initial treatment or salvage programs) was 4:1 (P < 0.001), suggesting that older patients with ovarian cancer are less likely to be referred for secondary experimental programs than for initial treatment. CONCLUSIONS: These data suggest that there are major differences between the presentation and treatment strategies of older compared to younger patients with ovarian cancer.

Adult↗
PubMed1993

Acute toxicity during external-beam radiotherapy for localized prostate cancer: comparison of different techniques.

PURPOSE: The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beam's eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. METHODS AND MATERIALS: We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beam's eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). RESULTS: Acute side effects gradually increased from week 1 through weeks 4-5 and generally declined or plateaued after that. The incidence of acute toxicities was significantly less with the beam's eye view/based technique than with the other two methods. For instance, the percentages of Grade 2 acute genitourinary toxicities for Groups A, B, and C were as follows: Week 1-0, 0, 0; Week 2-6, 0, 0; Week 3-6, 9, 2; Week 4-12, 14, 9; Week 5-35, 14, 9; Week 6-31, 16, 7; Week 7-33, 8, 8, respectively. The p values associated with differences in acute genitourinary toxicities for Weeks 1-7 using chi-square test were 0.072, 0.627, 0.389, 0.538, 0.123, 0.06, and 0.012; the p values for acute gastrointestinal toxicities were 0.512, 0.09, 0.031, 0.031, 0.003, < 0.0001, and 0.004, respectively. Pairwise comparison (Wilcoxon rank-sum test) showed statistically significant lower acute toxicity in Group C than Group B (e.g., p values, Weeks 1-7 for gastrointestinal toxicity: 0.633, 0.056, 0.010, 0.014, < 0.0001, < 0.0001, and < 0.0001, respectively) in the latter part of the treatment course. No correlation was found between the extent of toxicity and the patient age or the overall treatment time. Also, no correlation was found between the degree of toxicity and the radiation dose and fraction size, within the narrow ranges used (65-70 Gy and 180-200 cGy, respectively). A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen. CONCLUSION: The findings in this retrospective study need to be confirmed by other prospective studies.

Acute Disease↗
PubMed1993

Evidence for persistence of mitoxantrone within the peritoneal cavity following intraperitoneal delivery.

In clinical trials examining the intraperitoneal (ip) administration of mitoxantrone as therapy of platinum-refractory small-volume residual ovarian cancer, the characteristic "blue color" of the agent has been demonstrated to stain the surface of the peritoneal cavity and to persist for > or = 1 month following the last course of therapy. To determine if this blue staining material contains potentially cytotoxic concentrations of mitoxantrone, we analyzed tissue obtained at exploratory laparotomy in six women who had last received the agent administered ip from 6-22 weeks prior to surgery. Concentrations of mitoxantrone ranged from < 0.1 to 13.8 micrograms/g of tissue examined. Since any mitoxantrone present on the peritoneal surface will be highly protein bound, any residual drug may not have cytotoxic potential. The dose-response curves of mitoxantrone in a human clonogenic cytotoxicity assay against the RPMI 2780/S human ovarian cell line were virtually identical when the cells were incubated in either 5 or 50% fetal bovine serum, suggesting that protein binding will not significantly impair mitoxantrone-induced tumor cell killing. We conclude that the ip administration of mitoxantrone may lead to prolonged exposure of surface tumor to the high local concentrations of the active cytotoxic agent. This effect may contribute significantly to the antineoplastic potential of ip mitoxantrone in patients with small-volume residual ovarian cancer.

Dose-Response Relationship, Drug↗
PubMed1993

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.

Adult↗
PubMed1993

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.

Adult↗
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

The flipped meniscus sign.

Meniscal fragments may be difficult to detect on magnetic resonance (MR) imaging and yet are clinically significant. This paper describes and illustrates the MR appearance of an easily overlooked meniscal fragment. Ten knees, each appearing to show an abnormally large anterior meniscal horn (8 mm or more in height) were prospectively identified on MR images. In each case demonstrable large tears of the ipsilateral posterior horns were present (same meniscus as had large anterior horns). The lateral meniscus was involved in nine cases and the medial in one. Two of the ten patients imaged had surgically proven bucket-handle meniscal tears as well as meniscal fragments overlying the ipsilateral anterior horn. In one case previous MR imaging at our institution had demonstrated the affected anterior horn to be of normal caliber. The striking MR appearance of an abnormally enlarged anterior meniscal horn in association with a tear of the ipsilateral posterior horn suggests the presence of a meniscal fragment or of a posteriorly detached bucket-handle tear of the posterior horn of the meniscus.

Female↗
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

Comparison of CT-based treatment planning and retrograde urethrography in determining the prostatic apex at simulation.

In 20 consecutive patients who underwent treatment planning, localization of the prostatic apex with CT-based techniques at simulation was compared to location of the apex as defined by retrograde urethrography. In addition, the location of the urethrogram-defined prostatic apex was compared with the bottom of the ischial tuberosities, which is often recommended as the inferior margin of the field. In 15% of the patients there was agreement between the CT-defined apex and the urethrogram-defined apex; in 85% there was discordance. In a majority of patients with discordance, the urethrogram apex was located caudad to the CT-defined apex (71%) with a median difference of .65 cm. In 29% of the patients the urethrogram apex was located superior to the CT-defined apex. Overall, 75% of the patients had discordance between the urethrogram apex and the CT apex of 0.5 cm or greater; 30% had an absolute difference of 1.0 cm or greater. Comparing the location of the prostatic apex with the bottom of the ischial tuberosities revealed that in 15% of the patients the apex was 1.0 cm or less from the bottom of the tuberosities and in 45% it was less than 1.5 cm. This would place the apex of the prostate in the penumbra region of the field and risk undertreatment of the prostate if the bottom of the ischial tuberosities was the inferior margin of the field. Measuring the location of the prostatic apex from the top of the symphysis pubis revealed that a distance of 4.9 cm encompassed the apex in all 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1993

Teaching medical diagnosis: a rule-based approach.

This paper discusses the design of a diagnostic process simulator which teaches medical students to think clinically. This was possible to achieve due to the application of a rule-based approach to represent diagnosis and treatments. Whilst using the simulator, as a result of the student's incorrect and correct decisions, the clinical situation changes accordingly. New diagnostic options result in the ability to choose further clinical and laboratory tests. The simulator is being implemented on Sun workstations and Macintosh computers using Prolog programming language.

Clinical Competence↗
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↗