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Biomedical subjects

S Rubin

Publications and source records attributed to S Rubin.

At least 19 recordsLinked to original sources
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

Rita Kennedy: case analysis for decision-making.

For nurse educators, the teaching environment has changed drastically. During the past two decades, the pressures of public, professional and educational accountability have impacted on the nursing instructor. Clinical teaching of student nurses has not escaped these pressures and poses concerns for nursing instructors. The Rita Kennedy case illustrates some of today's issues. To illustrate some of the difficulties in dealing with such issues, the case will be analysed using the Schnelle's model. Although Schnelle's framework was initially used for analysis for business cases, the framework for analysis and decision-making is also applicable in nursing education. The following analysis will first discuss assumptions, followed by an alternative course of action, decision and recommendation. However, to assist understanding, the information in the Kennedy case has been categorised in the Table.

Decision Making↗
PubMed1992

Practical applications of Beam's Eye View-based treatment planning to head and neck sites.

Because of the complex anatomy of the structures involved by tumor as well as of the critical normal structures, treatment planning for advanced or spatially irregular cancers of head and neck sites is often extremely challenging. Computerized axial tomographic scanning is frequently invaluable in delineating tumor extension into areas inaccessible to physical examination. Our Beam's Eye View Planning (BEVP) capability allows us to incorporate this radiographic information accurately into actual plans used in the clinic. Over the past 2 1/2 years, we have applied this technique to 31 selected head and neck cancer patients at Michael Reese/University of Chicago Center for Radiation Therapy. Tumors were chosen on the basis of anatomical complexity: most involved multiple head and neck sites including orbit, skull base, paranasal sinuses and cavernous sinus. In all cases, radiation tolerance of critical normal structures including spinal cord, brain stem, optic chiasm, and eye had to be considered. With careful use of rigid immobilization devices and the outlining of several normal structures for purposes of alignment, we had no difficulty applying our BEVP technique to clinical simulations. Oblique field blocking was especially facilitated by BEVP. We found the BEVP technique very useful to assure that tumor coverage was adequate and tolerance of normal tissues not exceeded.

Computer Simulation↗
PubMed1992

Quantification of doses to mediastinal lymph nodes in Hodgkin's disease.

Hodgkin's disease is highly curable today. Radiotherapy (RT) is the treatment of choice in the early stages. A mantle field is often used in the RT of Hodgkin's disease, and the technique and dosimetry are quite complex. We used computerized tomography (CT)-based dosimetry to determine doses delivered to different mediastinal nodes with the commonly used technique in Hodgkin's disease that was originally described by Kaplan. We used dose-volume histograms to determine doses to various groups of nodes in nine patients. Significant inhomogeneity (30%, 30%, 35%, 35%, 30%, 40%, 35%, 35%, and 30% in the nine patients) in dose distribution was found within the mediastinum. With the advent of 3-dimensional CT-based treatment planning, we are able to quantify such inhomogeneities. The question arises whether a homogeneous, lesser dose can achieve equal results. Average doses and "effective doses" were also calculated. The "effective doses" in eight patients (for a prescribed dose of 44 Gy) with a midline posterior spinal cord block added at 20 Gy were 37.3 Gy, 34.3 Gy, 36.0 Gy, 38.4 Gy, 35.8 Gy, 38.1 Gy, 36.7 Gy, and 36.7 Gy, respectively. A homogeneous dose equivalent to effective dose may achieve the same control as an inhomogeneous dose delivery. Prospective 3-D dosimetric studies are required to confirm this concept.

Hodgkin Disease↗
PubMed1992

A dosimetric study comparing three-, four-, and six- field plans for treatment of carcinoma of the prostate.

We present a three-dimensional dosimetric analysis of 3-, 4-, and 6-field plans using 24 MV photon beams for treatment of carcinoma of the prostate. We compare isodose distributions on a transverse plane through the center of the target as well as differential and integral dose volume histograms for the target and critical structures, respectively. An extensive study on a representative case led to the development of a technique where two complementary 3-field daily plans deliver the same daily target dose as the standard 4-field box while affording sparing of the bladder and rectum similar to that achieved with a 6-field plan. This technique was shown to yield the same results on a sample of four additional patients representing a range of target and patient sizes. We conclude that the combined two-day, 3-field method for treatment of the prostate may be a better choice than the standard 4-field box or the 6-field daily plan for dose escalation studies.

Humans↗
PubMed1992

Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.

PURPOSE: There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting. PATIENTS AND METHODS: Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities. RESULTS: Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program. CONCLUSION: Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.

Acute Kidney Injury↗
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

Exploring the use of chronic low-dose oral etoposide in ovarian cancer: is there a role for this "new drug" in the management of platinum-refractory disease?

Despite showing high objective response rates (70% to 80%) to cisplatin- or carboplatin-based chemotherapy, most patients with ovarian cancer ultimately die of complications of their disease. Etoposide, given either as a single agent or in combination with the organoplatinum compounds, has produced disappointingly low response rates in the salvage setting. Based on recent data that suggest chronic administration of oral etoposide is superior to single daily dosing every 3 to 4 weeks, and the failure of previous trials to evaluate etoposide's activity in cisplatin-resistant malignancies, we have begun a phase II trial of chronic, low-dose oral etoposide in patients with clinically defined, platinum-resistant ovarian cancer. Thus far, 11 patients have been entered into the study. Neutropenia, the most prevalent toxicity, has precluded several patients from receiving the full 20-day course of 50 mg/d. No responses to treatment have been observed in nine evaluable patients. The study continues to accrue patients. The final results of this study and other trials should help determine the efficacy of chronic low-dose oral etoposide administration in patients with ovarian cancer.

Administration, Oral↗
PubMed1991

Persistent hypomagnesemia following cisplatin chemotherapy in patients with ovarian cancer.

The development of acute hypomagnesemia following cisplatin administration is a well-recognized complication associated with the use of this chemotherapeutic agent. However, there is limited information available in the medical literature concerning how long this abnormality may persist following the discontinuation of cisplatin. Of 13 patients with ovarian cancer who had a baseline serum magnesium determination obtained prior to the initiation of a second-line cisplatin-based chemotherapy regimen, 9 (69%) were found to be hypomagnesemic (serum magnesium less than 1.4 mg/l), including 3 patients with serum magnesium values less than 1.0 mequiv/l. The median cisplatin-free interval for these 9 patients was 19 months (range 6-40 months). We conclude that persistent, and possibly permanent, hypomagnesemia is common following cisplatin chemotherapy.

Cisplatin↗
PubMed1991

Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy.

Cisplatin is one of the most active single agents in the treatment of advanced cancer of the cervix. The concurrent administration of the nephroprotective agent, sodium thiosulfate, has enabled exploitation of the therapeutic potential of cisplatin. To explore the role of cisplatin dose intensity in the treatment of patients with cancer of the uterine cervix, patients with persistent/recurrent measurable disease were treated with cisplatin at 200 mg/m2 as a 2-hr infusion with sodium thiosulfate given at 3.3 g/m2 1 hr prior to cisplatin and 6.6 g/m2 during the cisplatin infusion. Treatment was repeated monthly. Due to the known cumulative toxicity of cisplatin, treatment beyond two cycles (400 mg/m2) was given only to those patients who had at least demonstrated a PR. Audiologic evaluation was done prior to each cycle of treatment. Eleven patients were entered with a median age of 43 years (range, 25-57), a median KPS of 80% (range, 60-90%), and nine epidermoid and two adenocarcinoma, and all patients had received previous pelvic irradiation. Twenty-eight cycles of treatment were given: 1, five cycles; 3, three cycles; 7, two cycles. No greater than or equal to 3+ hematologic, neurologic, or renal toxicity was demonstrated. Ototoxicity was demonstrated in the mild to moderate hearing loss range (3000-8000 Hz). The greatest threshold shift occurred after the first course of cisplatin. There were three PRs with a maximum duration of 4 months. Due to the significant toxicities encountered, the low response rate, and the limited duration of responses, this trial was closed early to accrual.

Adult↗
PubMed1991

Late effects of cisplatin-based chemotherapy on renal function in patients with ovarian carcinoma.

While the acute toxicity of cisplatin on renal function is well described, the long-term effects have received little attention in the medical literature. In an effort to examine this important issue, we evaluated the renal function of a group of 60 women with ovarian cancer who received a second-line cisplatin-based chemotherapy program at the Memorial Sloan-Kettering Cancer Center longer than 6 months following the completion of their initial cisplatin-based chemotherapeutic regimen. These patients had not received any cisplatin for a median of 19 months (range, 6-57 months) prior to beginning the second-line program. Only 4 patients (7%) had a serum creatinine value greater than 1.3 mg/dl (upper limit of normal in our laboratory) at the time of initiation of the second-line program. In each case, the serum creatinine was less than or equal to 1.6 mg/dl. An additional 6 patients (10%) had a greater than 50% increase in serum creatinine above the initial baseline value prior to any treatment, but were still within the normal range. Following second-line cisplatin therapy, only 1 of the 60 patients (2%) experienced a serum creatinine rise to greater than 2.0 mg/dl. We conclude that a limited number of patients with ovarian cancer who are long-term survivors following cisplatin-based chemotherapy exhibit evidence of a mild persistent compromise of renal function and, in general, second-line cisplatin can be administered to previously treated patients without the development of serious renal dysfunction.

Adult↗
PubMed1991

Celiac axis and superior mesenteric artery injury associated with left radical nephrectomy for locally advanced renal cell carcinoma.

The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions.

Carcinoma, Renal Cell↗