Biomedical subjects

B Reichman

Publications and source records attributed to B Reichman.

At least 91 records · Page 5Linked to original sources

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

Chemotherapy-induced neutropenia and fever in patients receiving cisplatin-based chemotherapy for ovarian malignancy.

Fifty-six episodes of chemotherapy-induced neutropenia and fever occurred in forty-three patients receiving cisplatin-based combination chemotherapy for ovarian cancer. All patients were treated with broad-spectrum antibiotics including gentamicin. Twelve of fifty-six episodes were associated with positive cultures; in six patients a single organism was isolated, and the other six patients had polymicrobial infection. The mean duration of antibiotic therapy was 6.5 days. One patient died of sepsis. Fifty-five episodes had a successful outcome. There was no antibiotic-related morbidity. Based on this review we recommend broad-spectrum antibiotic therapy for chemotherapy-induced neutropenia with fever. The regimen of gentamicin plus ticarcillin and clavulanic acid (ceftazidime for penicillin-allergic patients) is effective as initial therapy. Additional agents (i.e., vancomycin) may be necessary in culture-positive patients based on sensitivity testing of bacterial isolates. Gentamicin can be safely administered to patients receiving cisplatin-based chemotherapy without compromising ability to continue cisplatin therapy in subsequent treatment cycles.

Adult↗

PubMed1991

Intraperitoneal chemotherapy: analysis of complications with an implanted subcutaneous port and catheter system.

To determine the morbidity associated with delivery of intraperitoneal chemotherapy via subcutaneous semipermanent infusion catheters, we analyzed the data on 227 patients treated from April 1985 through December 1989. A total of 249 catheters were inserted and used to administer chemotherapy in these patients. There were 40 (17.6%) complications associated with the use of 230 original catheters, with 20 patients experiencing catheter inflow obstruction and 20 developing catheter-related infections; the latter group included 8 patients with bowel perforations. Although there was a trend toward an increase in catheter-related infections in association with large bowel surgery and appendectomies, sample size limited statistical analysis. There were 7 (36.8%) complications associated with the use of 19 replacement catheters. This rate was significantly increased (P = 0.03) when compared with the complication rate of original catheters. This system functions well and has an acceptable level of morbidity for delivery of intraperitoneal chemotherapy in gynecologic cancer patients.

Catheterization↗

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

Prognostic factors for recurrence following negative second-look laparotomy in ovarian cancer patients treated with platinum-based chemotherapy.

Prior studies of the risk of recurrence following negative second-look laparotomy have included patients treated with a variety of chemotherapeutic regimens, including nonplatinum regimens. We have examined the long-term outcome and risk factors for recurrence among a homogeneous group of platinum-treated patients. During the years 1978-1987, 91 patients at Memorial Sloan-Kettering Cancer Center had a negative second-look laparotomy following platinum-based chemotherapy for epithelial ovarian cancer. The mean age at diagnosis was 57 years, with a range of 30 to 79. Distribution by stage was as follows: I, 10; II, 18; III, 57; IV, 6. The mean number of cycles of platinum prior to second-look surgery was 6.3. The mean number of biopsies taken at negative second-look laparotomy was 12. Lymph node biopsies were done in 47/91 (52%) of patients. Median follow-up from the date of second-look laparotomy was 54.6 months among survivors. Forty of ninety-one patients (44%) have had recurrence, almost 40% of which were outside the peritoneal cavity. The mean interval from negative second-look laparotomy to recurrence was 24 months (range, 2-70 months). By multivariate analysis the risk of recurrence was significantly related to stage (P = 0.017), histologic grade (P = 0.041), and the amount of tumor remaining after the first operation for ovarian cancer (P = 0.015). Recurrence by stage was as follows: stage I, 1/10 (10%); stage II, 5/18 (28%); stage III, 31/57 (54%); stage IV, 3/6 (50%). Recurrence by grade was as follows: grade 1, 4/18 (22%); grade 2, 11/28 (39%); grade 3, 25/45 (56%). There was no relationship between the risk of recurrence and the number of cycles of platinum, the number of biopsies performed at second-look, or the number of months from primary surgery to second-look. Patients having negative second-look laparotomy following platinum-based chemotherapy for advanced epithelial ovarian cancer have a substantial risk of recurrence, particularly within the first 3 years. Such patients should be offered participation in clinical trials of consolidation therapy directed against both intraperitoneal and extraperitoneal disease.

Adult↗

PubMed1991

Cisplatin-based combination chemotherapy in carcinoma of the fallopian tube.

Forty-three cases of primary tubal adenocarcinoma were treated at Memorial Sloan-Kettering Cancer Center between 1979 and 1989. Thirty-eight patients who received cisplatin-based combination chemotherapy following primary surgery were reviewed. The mean patient age was 59 years, with 86% postmenopausal. Distribution by stage was as follows: I, 3 (7%); II, 4 (11%); III, 27 (71%); and IV, 4 (11%). Median follow-up from the time of diagnosis was 62 months (range, 5-132). Overall survival for all 38 patients by Kaplan-Meier analysis was 51% at 5 years. Excluding stage I, patients with no residual disease following surgery had a significantly higher 5-year survival (83%) than those left with gross residual disease (28%). Twenty-six patients underwent a second-look procedure. Of the 21 patients with advanced (stages III, IV) disease undergoing reexploration, 11 (52%) had a negative second-look and 10 (48%) were positive. Ten of the eleven patients with a negative second-look remain clinically free of disease with a median follow-up of 49 months. One patient with stage III disease had recurred after 47 months. Carcinoma of the fallopian tube appears to respond favorably to cisplatin-based multiagent chemotherapy. Patients with advanced-stage disease who achieve a negative second-look appear to have an improved possibility of remaining disease-free over similar-stage patients with ovarian cancer.

Adult↗

PubMed1991

Haemodynamic effects of recombinant interleukin-2 administered by constant infusion.

Adoptive immunotherapy with recombinant interleukin-2 (rhIL-2) has been reported to induce tumour regression in some patients with refractory cancer. However, the cardiovascular toxicity of bolus therapy requires invasive monitoring of patients in the intensive care unit (ICU). In an effort to examine the haemodynamic alterations caused by a constant infusion of IL-2, as opposed to bolus therapy, we studied the haemodynamic variables of 10 patients, with no evidence of heart disease, receiving 3 x 10(6) IU/m2 per day of rhIL-2 as a continuous infusion for 5 days. Measured and derived haemodynamic variables were obtained immediately prior to, at 2, 24, and 48 h during, and upon termination of the infusion. There was no evidence of clinical haemodynamic instability in these patients. Except for development of fever and tachycardia, there were no clinically significant differences in any measured or derived haemodynamic parameter. Moreover, continuous electrocadiographic monitoring of these patients during the infusion did not reveal any abnormalities. Invasive haemodynamic monitoring in an ICU is not necessary in carefully selected patients receiving constant infusion rhIL-2, at the described dose and schedule.

Adult↗

PubMed1991

Extrahepatic biliary system cancer: an update of a combined modality approach.

Since January 1985, 12 patients with local/regional extrahepatic biliary system cancer (2: gallbladder; 5: Klatskin; and 5: common bile duct) underwent combined modality therapy. An endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiogram, and biliary drainage were performed in 5 patients, and 7 patients underwent laparotomy and biopsy or subtotal resection. All patients initially received 5,000 cGy to the tumor bed and primary nodal area and 10 received an additional 1,500-cGy boost to the tumor bed. Chemotherapy (5-fluorouracil/mitomycin-C) was delivered at the beginning of each radiation treatment course. Four patients received an additional 1-4 cycles of maintenance chemotherapy and 7 received a boost with brachytherapy. The median survival was 17 months and the overall 4-year actuarial survival was 36%. Four patients have no evidence of disease at 16, 30, 48, and 64 months, respectively. The patterns of failure as a component of failure were local/regional progression, 50%; abdominal failure, 58%; and distant failure, 8%. Of the 8 patients who developed failure, 6 developed a component of local/regional progression. Our data continue to show that this approach is feasible and may result in an improvement in survival. Continued follow-up will be needed to determine the ultimate impact of this aggressive approach.

Adenocarcinoma↗

PubMed1991

Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin.

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma.

Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma. To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease. The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%). Three patients declined surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules. IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease.

Adult↗

PubMed1991

Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin.

In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program. Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs). The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs. Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy.

Adult↗

PubMed1991

Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer.

Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation).

Adult↗

PubMed1991

[Children of incest].

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Congenital Abnormalities↗

PubMed1990

Lenticulostriate vasculopathy in infants with infections of the central nervous system sonographic and Doppler findings.

Eleven infants had echogenic stripes in the basal ganglia at the location of the lenticulostriate arteries, seen by head ultrasound. Eight patients had proven infection with rubella (2 patients), cytomegalovirus (2 patients), syphilis (1 patient) or bacterial meningitis (3 patients). Two had probable intrauterine infection clinically, but the organism could not be identified; one had trisomy 13. A recent report correlated these echogenic stripes in patients with viral and syphilitic intracranial infection with pathologically proven mineralizing vasculopathy. Our group manifests a wider range of intracerebral infection associated with this finding. Duplex sonography performed in four infants showed these stripes in vivo to be arteries in the basal ganglia. The lenticulostriate arteries are not normally visible by grey scale sonography but their Doppler signal may be elicited in normal children and they are rendered vividly visible by color Doppler. Echogenicity of these vessels is highly suggestive of intracranial infection because it is not encountered normally or in babies with non infectious intracranial disorders except trisomy 13. The prognostic significance of this finding is yet to be determined.

Arteries↗

PubMed1990

Aggressive chemosurgical debulking in patients with advanced ovarian cancer.

From July 1986 to June 1989, 43 evaluable patients with advanced ovarian cancer were treated on protocol with initial cytoreductive surgery, two courses of high-intensity intravenous Cytoxan (1000 mg/m2) and cisplatin (120-200 mg/m2) chemotherapy, and repeat debulking laparotomy in an effort to maximize response to a subsequent four cycles of intraperitoneal platinum-based chemotherapy. Two patients were stage IIIA, 2 stage IIIB, 28 stage IIIC, and 11 stage IV. Five tumors were grade 1, 9 grade 2, and 29 grade 3. Thirty-eight (88%) patients had bulky tumor (5-25 cm) found at first laparotomy; 25 of these had greater than 1-cm residual after initial debulking. Following two cycles of intensive intravenous chemotherapy 18 of these 25 had greater than 1-cm disease found at second laparotomy; 12 of 18 underwent secondary cytoreduction to less than 1 cm. Thus, 30 of these 38 (79%) patients entered the intraperitoneal phase of the protocol with less than 1-cm disease. Four patients had 2- to 5-cm tumor at initial laparotomy; two of four were debulked to less than 1-cm residual. All four were found to have less than 1-cm disease at second laparotomy. This combination regimen was well tolerated. There was one treatment-related death. In sum, 42 of 43 patients had tumor greater than 2 cm at staging laparotomy and 38 (88%) had large, bulky disease (5-25 cm); 34 of 43 (79%) entered the intraperitoneal phase of the protocol with optimal (less than 1-cm) disease. Aggressive chemosurgical cytoreduction in patients with bulky advanced ovarian cancer can leave a large proportion of patients with minimal residual disease and maximize their chances of responding to subsequent intraperitoneal chemotherapy.

Cisplatin↗

PubMed1990

Combined modality therapy of extrahepatic biliary system cancer.

From January 1985 to December 1988, 10 patients with local/regional extrahepatic biliary system cancer (gallbladder: 2, Klatskin: 4, common bile duct: 4) underwent combined modality therapy. Laparotomy and biopsy or subtotal resection were performed in six patients and endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiogram, and biliary drainage in four patients. Patients initially received 5000 cGy to the tumor bed and primary nodal area. Eight received an additional 1500 cGy boost to the tumor bed. Chemotherapy (5-FU/mitomycin-C) was delivered at the beginning of each radiation treatment course. Four patients received an additional 1-4 cycles of maintenance chemotherapy and six received a boost with brachytherapy. The mean survival was 32 months and the median survival was 16 months. Five patients are currently NED at 16, 17, 17, 48, and 52 months. The overall 3-year actuarial survival was 50%. The cumulative incidence of failure as a component of failure was local/regional: 50%, abdominal: 40%, and distant: 10%. Of the five patients who developed failure, all developed a component of local/regional failure. Our data show that this approach is feasible and offers similar results to those reported in the literature. However, further follow-up will be needed to determine if this combined modality approach offers improved local control and survival rates compared with surgery or biliary bypass/drainage alone.

Biliary Tract Neoplasms↗

PubMed1990

Choledocholithiasis in infants: diagnostic and therapeutic problems.

During the 3-year period, January 1986 through December 1988, 7 of 24 infants evaluated for cholestatic liver disease were found to have choledocholithiasis with or without associated gallbladder disease. Five were born prematurely with associated predisposing factors, especially systemic infection and total parenteral nutrition. The clinical course varied from spontaneous recovery in two patients to ongoing liver disease requiring surgical or endoscopic intervention in five infants. Asymptomatic patients with normal liver function and persistently dilated extrahepatic biliary trees posed the most difficult therapeutic problems. Endoscopic retrograde cholangiography appeared to be an effective and rewarding therapeutic approach.

Biliary Tract↗

PubMed1990

Phase II trial of intraperitoneal mitoxantrone in the management of refractory ovarian cancer.

To define both the toxicity and efficacy of intraperitoneal mitoxantrone in the treatment of refractory ovarian carcinoma, 31 patients were entered onto a phase II trial of this agent delivered in a 2 L treatment volume on a monthly basis. Due to excessive local pain at the initial dose level (30 mg/m2), the amount of drug delivered with each treatment course was reduced to 20 mg/m2. Despite this reduction, 74% of patients required narcotic analgesia during treatment. In addition, there were four episodes of bowel obstruction (one requiring surgical intervention) during therapy, and two patients developed bowel obstruction and intraabdominal abscesses following the completion of treatment. Six of 18 evaluable patients (33%) whose largest tumor diameter was less than or equal to 1 cm at protocol initiation experienced surgically documented responses, compared with one of 11 patients (9%) whose largest tumor was greater than 1 cm in diameter. If the two patients exhibiting what we called a mixed response to treatment are included, seven of 21 patients previously treated with intraperitoneal cisplatin responded to this treatment program, including four patients who had failed to respond to intraperitoneal cisplatin. No responding patient has demonstrated clinical evidence of relapse with a median follow-up of 7 months (range, 3+ to 13+ months) from response laparotomy. Intraperitoneal mitoxantrone is an active treatment program in patients with small-volume refractory ovarian carcinoma, but local toxicity can be severe. Due to the toxicity encountered with this specific program, its use cannot be recommended for standard clinical practice. However, in view of the activity observed in refractory ovarian carcinoma, including responses in patients who had previously failed intraperitoneal cisplatin, it is important to continue to explore alternative therapeutic regimens using intraperitoneal mitoxantrone to reduce local toxicity while maintaining or improving efficacy.

Carcinoma↗