PubMed Health⌕ Search

Biomedical subjects

B Reichman

Publications and source records attributed to B Reichman.

At least 73 records · Page 4Linked to original sources
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

Basal and meal-stimulated pepsinogen secretion in preterm infants: a longitudinal study.

In order to establish longitudinal normal values for basal and meal-stimulated pepsinogen secretory function in preterm infants, we studied 44 preterm infants with gestational ages of 28-36 weeks during the period of nasogastric tube feeding. Three age groups were evaluated: gestational ages of 28-30, 31-33, and 34-36 weeks. Basal pepsinogen did not change with postnatal age in any of the groups. Significant meal-stimulated pepsinogen secretion appeared during the third postnatal week in infants of 28-30 weeks of gestation. In the groups of infants of 31-33 and 34-36 weeks of gestation, significant meal-stimulated pepsinogen secretion was apparent in the first postnatal week. This study suggests that maturation of pepsinogen secretion appears at 31 weeks of gestation, independent of early feeding.

Gastric Mucosa↗
PubMed1992

Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy.

PURPOSE: To determine if fluorouracil (5-FU) plus high-dose leucovorin (LV) enhances local response in patients receiving preoperative radiation therapy (RT) for adenocarcinoma of the rectum, we compared the degree of downstaging in patients receiving preoperative RT with or without chemotherapy. PATIENTS AND METHODS: For this comparison, three groups of patients who were treated with identical doses and techniques of preoperative pelvic RT (total dose of 5,040 cGy) were examined. Group 1 included 20 patients with unresectable disease who received combined RT and LV/5-FU. Group 2 included 11 patients with unresectable disease who received preoperative RT. Group 3 included 21 patients with invasive, resectable, primary disease who received preoperative RT. RESULTS: Patients with unresectable disease who received LV/5-FU had a higher rate of pathologic complete response (20% v 0%) and a lower incidence of positive nodes (30% v 64%) compared with those who did not receive chemotherapy. Even when the most favorable group of patients was included (group 3), patients who received LV/5-FU still had a higher complete response rate (20% v 6%) and a lower incidence of positive nodes (30% v 53%) compared with those who received RT without LV/5-FU. Of those patients with initially unresectable disease, the resectability rate was higher in those who received LV/5-FU compared with those who did not receive LV/5-FU (90% v 64%). Patients who received LV/5-FU experienced slightly more grade 1 to 2 fatigue, stomatitis, nausea, and grade 3 diarrhea, tenesmus, and dysuria. CONCLUSIONS: Despite the fact that patients who received chemotherapy (group 1) had more advanced disease compared with those with resectable disease (group 3), the addition of LV/5-FU increased the resectability and downstaging rates. The ultimate impact of a complete response as well as a decrease in the incidence of pelvic nodes on local control and survival remains to be determined. However, given the enhancement of down-staging in patients with unresectable rectal cancer, we are encouraged by the combined modality approach.

Adenocarcinoma↗
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

Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach.

PURPOSE: We compared the combined radiation therapy (RT) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT, fluorouracil (5-FU), and high-dose leucovorin (LV) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer. PATIENTS AND METHODS: Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5-FU. Patients with resectable disease received identical doses, techniques, and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively. On day 1, patients received LV and 5-FU times one cycle. RT began on day 8. A second cycle of LV and 5-FU was given concurrently with the fourth week of RT. RESULTS: Although more patients (75% v 32%; P = .02) received the higher dose level of 5-FU (250 mg/m2), significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy (13% v 48%; P = .045). There was no grade 3 to 4 myelosuppression in either group. The two grade 3 toxicities in the preoperative group were gastrointestinal. The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary; four patients had a grade 4 toxicity. CONCLUSION: Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach.

Adult↗
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

The effect of thyroxine and corticosteroids upon amniotic fluid fluorescence polarization: a randomized controlled study.

The efficacy of glucocorticoid and intra amniotic thyroxine therapy on fetal lung maturity were compared in a randomized prospective clinical trial. Eighty two patients received either intra amniotic thyroxine (n = 36), or intra muscular Dexamethasone (n = 46). The Fluorescence Polarization (FP) of amniotic fluid measured prior to and one week following treatment were similar in the two groups. The rate of decrease in FP value per unit of time (dFP/dt) was identical in the T4 and corticosteroid treated patients and the proportion of immature FP values obtained was similar in the two groups. The effect of thyroxine therapy was more pronounced in pregnancies above 33 weeks gestation. Intra amniotic thyroxine therapy appeared to be as effective as glucocorticoids for the enhancement of fetal lung maturity. This therapeutic modality may be of particular use on pregnant subjects in whom a relative contra indication for the administration of steroids exists.

Amniotic Fluid↗
PubMed1992

Pharmacokinetic study of intraperitoneal streptozotocin.

Streptozotocin, a nitrosourea, has limited antitumour activity. However, in concentrations and exposures higher than those achieved after intravenous dosing, streptozotocin has been reported to sensitize various cell lines in vitro to other nitrosoureas or alkylating agents. We hypothesized that the intraperitoneal administration of streptozotocin would achieve concentrations and exposures in the peritoneal cavity sufficient for this sensitization to take place. The pharmacokinetics of streptozotocin in the peritoneal cavity and in plasma were determined in patients who received 1 g of streptozotocin via the intraperitoneal route. Fifteen courses were administered to 12 patients. The mean total area under the concentration versus time curves (AUC) was 183 +/- 31 (SE) mM min in the peritoneal cavity (5 courses) and 5.3 +/- 1.1 (SE) mM min in plasma (6 courses). The mean peritoneal to plasma AUC ratio was 64 +/- 23 (5 courses). The mean peak streptozotocin concentrations in the peritoneal cavity (5 courses) and plasma (6 courses) were 1.9 +/- 0.4 mM and 0.03 +/- 0.01 mM, respectively. No significant toxicity was observed on any course. We conclude that intraperitoneal administration of streptozotocin is feasible, and that drug concentrations and exposures are in an appropriate range in the peritoneal cavity to cause sensitization to other nitrosoureas.

Adult↗
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

New form of postaxial acrofacial dysostosis?

We report on a 2-month-old Sephardic Jewish girl with bilateral and symmetrical deficiency of the fifth digital rays of all 4 limbs, combined with severe deformations and other malformations of the limbs. These findings were associated with orofacial malformations, as well as with visceral anomalies differing from those found in other postaxial deficiency syndromes. Parents were closely consanguineous. We assume this patient represents a new form of postaxial acrofacial dysostosis.

Abnormalities, Multiple↗
PubMed1991

Preoperative high-dose leucovorin/5-fluorouracil and radiation therapy for unresectable rectal cancer.

Twenty patients with primary or recurrent unresectable rectal cancer limited to the pelvis were entered on a Phase I trial of preoperative pelvic radiation therapy (RT) (5040 cGy) and two cycles of combined high-dose leucovorin (LV) and 5-fluorouracil (5-FU), followed by surgery and ten cycles of postoperative LV/5-FU (sequential). Maximum tolerated doses (MTD) were determined for preoperative combined LV/5-FU and RT and for postoperative sequential LV/5-FU. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were combined LV/5-FU and RT (200 mg/m2) and sequential LV/5-FU (325 mg/m2). The median follow-up time was 14 months. The resectability rate was 89%, and the pathologic complete response rate was 21%. The MTD for combined LV/5-FU and RT was 300 mg/m2; therefore, the recommended dose of 5-FU is 250 mg/m2. The recommended dose of 5-FU for sequential LV/5-FU is 375 mg/m2. The dose-limiting toxicities in this trial were diarrhea, tenesmus, increased bowel movements, dysuria, and myelosuppression. For the six patients who received 5-FU at the recommended dose level, the median low counts were leukocyte count, 3.7/microliters (range, 2.4 to 4.9/microliters); hemoglobin, 9.0 g/dl (range, 8.2 to 11.9 g/dl); and platelet count (X1000), 146/microliters (range, 89 to 182/microliters). The incidence rate of any Grade 3 toxicity was 17% (diarrhea and frequent bowel movements). The recommended doses of 5-FU used in this protocol were well tolerated. Because there was a long delay before optimal doses of 5-FU could be delivered, the authors do not recommend that high-dose LV be used in conjunction with combined 5-FU and RT with the treatment regimen as currently designed. However, because the resectability and complete response rates were higher than those previously reported for preoperative RT alone, the authors are encouraged by the combined technique approach. New trials are currently being undertaken to determine if the use of a low-dose LV regimen is more tolerable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Induction of fetal lung maturation with intra-amniotic thyroxine in multiple pregnancy.

Two premature triplet pregnancies underwent repeated treatment aimed at acceleration of individual fetal lung maturity while administering intravenous tocolytic treatment. From the early third trimester, repeated amniocenteses were used for intra-amniotic administration of thyroxine to each sac, while the individual fetal lung maturation rate was determined by surfactant microviscosity until lung maturity was achieved.

Adult↗
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-1 trial of high-dose intravenous cisplatin with simultaneous intravenous sodium thiosulfate.

Previous pharmacological and clinical data have suggested that it is possible to increase significantly the dose of "active" cisplatin delivered systemically by the simultaneous administration of intravenous sodium thiosulfate. In order to define more critically the toxicity and potential efficacy of this therapeutic approach, 36 patients with a variety of solid tumors and limited pretreatment were entered into a phase-1 trial of high-dose intravenous cisplatin plus sodium thiosulfate. The maximally tolerated dose of cisplatin was found to be 200 mg/m2, excessive renal toxicity being observed at a dose of 225 mg/m2 (6/14 courses associated with serum creatinine rise to greater than 2.0 mg-%). Following several courses of high-dose cisplatin, peripheral neuropathy becomes the limiting toxicity (9/15 patients receiving at least three courses of cisplatin at greater than or equal to 150 mg/m2 experienced at least grade-1 neuropathy). Significant ototoxicity developed after only one or two treatment courses, but with continued treatment hearing loss appeared to stabilize in the moderately severe range in most patients. Major responses (PR/CR) were observed in 7/27 evaluable patients. We conclude that cisplatin can be administered at a dose at 200 mg/m2 as a 2-h infusion (with simultaneous sodium thiosulfate) with significant but acceptable toxicities and without evidence of loss of anti-neoplastic activity (secondary to the presence of thiosulfate). However, owing to the development of neurotoxicity most patients will be unable to receive more than three courses of this high-dose treatment regimen.

Adult↗