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Biomedical subjects

A R Paul

Publications and source records attributed to A R Paul.

16 recordsLinked to original sources
PubMed1993

Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A Phase II Study.

BACKGROUND: Low resectability rate and high locoregional recurrence are major factors contributing to the failure of surgical treatment for localized pancreatic adenocarcinoma. A Phase II study involving preoperative 5-fluorouracil (5-FU) and mitomycin C and radiation therapy was evaluated. METHODS: Thirty-one patients with biopsy-proven carcinoma (24, head of pancreas; 2, body; 5 duodenum) were treated with preoperative radiation therapy, 5040 cGy (180 cGy/fraction, 5 days/week), concurrent with 5-FU, 1000 mg/m2/day continuous infusion (days 2-5, 28-32) and mitomycin C 10 mg/m2 bolus (day 2). Ten patients had previous laparotomy or bypass surgery and were deemed unresectable; 21 had percutaneous, endoscopic retrograde choleangiopancreatic, or transhepatic stent biopsies. RESULTS: Toxicity included neutropenic fever (2 patients), biliary sepsis (2 patients), and nausea and vomiting requiring total parenteral nutrition. One patient died of biliary sepsis before completion of chemoradiation and 11 patients showed evidence of metastatic disease (clinical or occult). Resectability rate was 38% (10/26) for pancreatic carcinoma and 80% (4/5) for duodenal carcinoma. Pathology of the resected specimens revealed extensive necrosis and hyalinization with clear margins in all cases. Lymph node metastases were found in one case of pancreatic carcinoma. The four resected duodenal carcinomas contained no residual tumor in the specimens. At a median follow-up of 29 months, the median survival time for those with pancreatic carcinoma was not yet reached in the resection group and was 8 months in the nonresection group. The corresponding actuarial 5-year survival rates were 58% and 0%, respectively. CONCLUSIONS: Neoadjuvant chemoradiation therapy was given safely to patients with pancreatic and duodenal carcinoma. It facilitated complete resection in 38% of patients with pancreatic carcinoma and 80% of those with duodenal carcinoma. A significant downstaging of positive margins and regional lymph nodes occurs as a result of preoperative chemoradiation.

Adenocarcinoma↗
PubMed1993

A single institutional experience with preoperative chemoradiotherapy for stage I-III pancreatic adenocarcinoma.

In order to determine whether preresectional chemoradiotherapy (CTRT) would influence resectability, local control, and survival of patients with localized pancreatic adenocarcinoma, a 5 1/2-year prospective study of 39 patients treated with preoperative radiation therapy, 5-Fluorouracil (5-FU), and Mitomycin C has been performed. Thirty patients had celiotomy after CTRT (1/39 died while receiving CTRT, one refused surgery, and seven had extrapancreatic disease progression). Seventeen (57%) had resections (seven total, two distal subtotal, and eight Whipple pancreaticoduodenectomies). All had clear margins of excision, and only one had any positive lymph nodes in the resected specimen. Eleven patients with resection had Stage I cancers (5 T1b, 6 T2), five had Stage II, and one had a Stage III lesion. Previous bypass surgery, age, clinical response to CTRT, and tumor size had no influence on resectability. Two patients died postoperatively (12%) early in the series. Three others suffered major morbidity (chylous ascites requiring peritoneovenous shunt, ARDS, and prolonged afferent loop obstruction leading to a fatal liver abscess 5 months after surgery). Two patients with resection are alive without recurrence at 48 months after tissue diagnosis, and six others are also alive without recurrence, after from 6 to 23 months. In summary, resectability is probably enhanced and nodal metastases and resection margins are downstaged by preoperative CTRT. Demonstration of an improved survival benefit awaits further observation and phase III trials.

Adenocarcinoma↗
PubMed1992

Heterotopic mucinous cystadenoma of the pancreas.

A 46-year-old female who had been experiencing severe diarrhea and marked weight loss underwent exploratory laparotomy because of a mass near the tail of the pancreas noted on CT scan. Pathologic examination revealed a mucinous cystadenoma of the pancreas occurring in heterotopic pancreatic tissue. This is the second reported case of mucinous cystadenoma occurring in heterotopic pancreatic tissue.

Abdominal Neoplasms↗
PubMed1991

Phase II study of amonafide (nafidamide, NSC 308847) in advanced colorectal cancer.

Amonafide, a benzisoquinoline-1,3-dione with anti-tumor activity in preclinical screens, was administered to patients with recurrent or metastatic bidimensionally measurable colorectal cancer. Fourteen patients with no prior chemotherapy for advanced disease, performance status 0-1, and normal bone marrow, renal, and hepatic function were entered. Amonafide 300 mg/m2 was administered intravenously over 1 hour daily for five consecutive days; courses were repeated every three weeks. The major side effect was neutropenia: Grade 3 or 4 toxicity occurred in 5/14 patients. Other toxicities included nausea and vomiting, flulike symptoms, fever, rash and alopecia. Three patients had stable disease, but there were no responses observed. Amonafide at this dose and schedule has no activity in the treatment of colorectal cancer.

Adenine↗
PubMed1991

Long-term results of infusional 5-FU, mitomycin-C and radiation as primary management of esophageal carcinoma.

An analysis of the results of 90 patients with esophageal cancer treated prospectively with combined chemotherapy and radiation without surgery and with a median follow-up of 45 months is presented. Fifty-seven patients with Stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 hr) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Thirty-three patients received palliative treatment (5,000 cGy plus above chemotherapy) for Stage III, IV, or otherwise advanced disease (extraesophageal spread, distant metastases, multiple primary tumors). Follow-up ranged from 1 month to 96 months. Overall median survival of Stage I and II patients was 18 months with 3- and 5-year actuarial survival of 29% and 18%, respectively, while the median disease specific survival was 20 months with an actuarial disease specific survival of 41% and 30% at 3 and 5 years, respectively. A multivariate analysis of sex, histology, tumor location, and tumor size on survival revealed that the effect of stage was highly significant (Stage I versus II, 73% versus 33% at 3 years, p = .01), whereas the effect of sex approached significance (females versus males, 57% versus 34% at 3 years, p = less than .1). The actuarially determined local relapse-free rate for Stage I and II patients at both 3 and 5 years was 70%. Multivariate analysis again indicated stage to be highly significant (Stage I versus II, 100% versus 60% at 3 years, p = less than .01), whereas sex approached significance (female versus male, 75% versus 66% at 3 years, p = .07). The pattern of failure may be altered with this treatment regimen from local to one dominated by distant metastases. Of 29 patients who have failed, 14 (48%) had any component of local failure, whereas 21 (72%) had a distant failure as a component of failure. The median survival of patients with Stage III or IV disease was 9 months and 7 months, respectively. Palliation in this group of patients with advanced disease was good as 77% were rendered free of dysphagia post-treatment, and 60% were without dysphagia until death with a median dysphagia-free duration of 5 months. Severe toxicities were uncommon and nearly all were transient. Eleven of 90 patients (12.2%) had severe acute toxicities, whereas only 3 patients (3.3%) developed significant late treatment-related complications requiring hospitalization for management.

Adenocarcinoma↗
PubMed1990

Phase II study of biochemical modulation of fluorouracil by low-dose PALA in patients with colorectal cancer.

Higher response rates in colorectal cancer have been observed with regimens that increase the cytotoxicity of fluorouracil (5-FU) by altering the biochemical milieu at its site(s) of action. Phosphonacetyl-L-aspartate (PALA), which inhibits aspartate transcarbamylase and depletes uridine nucleotide pools in vitro and in vivo, selectively potentiates the antitumor activity of 5-FU in preclinical models. In a phase I/II study in patients with advanced colorectal cancer, PALA 250 mg/m2 was given on day 1, followed 24 hours later by 5-FU 2,600 mg/m2 by 24-hour infusion repeated weekly. Through the use of subcutaneous ports and portable infusion pumps, all patients were treated outside the hospital setting. Thirty-nine patients without prior chemotherapy received 884 courses of treatment. The primary site was colon in 31, rectum in eight. Toxicity was generally mild to moderate except among four patients who were escalated to 5-FU 3,250 mg/m2: two developed severe gastrointestinal toxicity and myelosuppression. Among the remaining 35 patients, gastrointestinal and neurologic toxicities predominated, but usually did not develop until the third or fourth month of treatment. Two patients were inevaluable for response. Among the 37 evaluable patients there were three complete and 13 partial remissions for a total response rate of 43% (95% confidence interval [Cl], 27% to 59%). The median duration of response was 5 months (range, 1.5 to 15 months). The projected mean survival is in excess of 17 months. This high response rate is comparable to the best results obtained with other means of modulation of 5-FU. Demonstration of a survival benefit will require larger phase III studies.

Adenocarcinoma↗
PubMed1988

Combined radiation and chemotherapy as primary management of adenocarcinoma of the esophagus and gastroesophageal junction.

Between January 1981 and December 1986, 20 patients with adenocarcinoma of the esophagus and gastroesophageal junction were entered into a prospective study involving combined radiation therapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin) as primary management. Nine patients with Stage I or II disease received definitive treatment consisting of 6000 cGy in 6 to 7 weeks and 5-FU (1000 mg/m2/24 hours) as a continuous intravenous (IV) infusion for 96 hours starting on days 2 and 29. Mitomycin (10 mg/m2) was administered as a bolus injection on day 2. Ten patients with extraesophageal and disseminated disease (Stages III and IV) and one patient with an unresectable anastomotic recurrence were considered palliative. Generally the palliative regimen did not differ from the definitive except for the radiation dose which in seven of the 11 patients was less than 6000 cGy (4000-5600 cGy). The range of follow-up was 6 to 74 months and no patient was lost to follow-up. Seven of the eight evaluable definitively treated patients were complete responders. The median relapse-free survival was 10 months and the median survival was 15 months in this group. In the palliative group, six of nine evaluable patients had relief of dysphagia until death or last follow-up with a median duration of 8 months. Our results indicate that combined modality treatment with infusional 5-FU, mitomycin, and radiation is an effective and well-tolerated treatment for adenocarcinoma of the esophagus and gastroesophageal junction. This treatment regimen offers palliation and some chance for cure to those patients who are inoperable, unresectable, or who refuse surgery.

Adenocarcinoma↗
PubMed1986

Treatment of advanced measurable or evaluable pancreatic carcinoma with 17-1A murine monoclonal antibody alone or in combination with 5-fluorouracil, adriamycin and mitomycin (FAM).

Between 1/85 and 3/86, 16 patients with advanced measurable or evaluable pancreatic carcinoma were treated with mouse monoclonal antibody consisting of a single dose of 400 mg 17-1A immunoglobulin given intravenously. None of the eight patients who received monoclonal antibody alone had any subjective or objective benefit. Two of the eight patients who received a combination of monoclonal antibody and 5-fluorouracil, adriamycin and mitomycin (F.A.M.) chemotherapy had clinically useful partial responses lasting 11 months and 7 months respectively. One of these patients, whose initial treatment consisted of an 8-week cycle of F.A.M. chemotherapy, had progressive deterioration as evidenced by weight loss and persistent abnormality of his CT scan, and then achieved a partial response following a single injection of monoclonal antibody while chemotherapy was continued. His response lasted 11 months. There was no toxicity associated with the administration of monoclonal antibody, and the F.A.M. chemotherapy was well-tolerated with moderate and acceptable hematologic toxicity and mild gastrointestinal side effects. There were no treatment-related deaths.

Adult↗
PubMed1985

Evaluation of bleomycin, chlorozotocin, MGBG, and bruceantin in patients with advanced soft tissue sarcoma, bone sarcoma, or mesothelioma.

Patients with objectively measurable soft tissue sarcoma, bone sarcoma, or mesothelioma who had failed at least one prior chemotherapy regimen received either bleomycin (20 U/M2 i.v. day 1 each week), chlorozotocin (150 mg/M2 i.v. q6 weeks), MGBG (500 mg/M2 i.v. each week, escalated in 50 mg/M2 weekly increments to a maximum dose of 700 mg/M2), or bruceantin (5.5 mg/M2 days 1, 8, 15, and 22, with cycles repeated every 6 weeks). One hundred eighty patients were evaluable: 53 on bleomycin, 51 on chlorozotocin, 38 on MGBG, and 38 on bruceantin. Two partial responses resulted from bleomycin, and one each from chlorozotocin and MGBG. Both responders on bleomycin had mesothelioma. Seventy-four percent of the patients were of ECOG performance status 0 or 1, and over half on each arm had moderate or worse toxicity. At these doses and schedules, none of the four drugs tested was active against previously treated sarcomas. Bleomycin, however, should be considered for further evaluation in mesothelioma patients.

Adolescent↗
PubMed1984

An Eastern Cooperative Oncology Group evaluation of combinations of methyl-CCNU, mitomycin C, Adriamycin, and 5-fluorouracil in advanced measurable gastric cancer (EST 2277).

In a prospectively randomized trial, patients with advanced locally recurrent or metastatic gastric adenocarcinoma were randomized to receive 5-fluorouracil (5-FU) and methyl-CCNU; 5-FU, Adriamycin (Adria Laboratories, Columbus, Ohio), and methyl-CCNU; 5-FU, Adriamycin, and mitomycin C; or Adriamycin and mitomycin C alone. One hundred eighty-three previously untreated evaluable patients were randomized among the four arms. An additional 39 patients previously treated with 5-FU, were assigned to treatment directly to Adriamycin and mitomycin C. Response rates were 14%, 29%, 39%, and 29%, respectively, among previously untreated patients and 21% for Adriamycin and mitomycin C among previously treated patients. 5-Fluorouracil, Adriamycin, and mitomycin C, the arm containing the largest number of responders (18), was the combination associated with the longest median survival. A larger proportion of patients in this arm survived one year or more. In addition, the 5-FU, Adriamycin, and mitomycin C program had the lowest rate of severe or worse toxicity of any of the treatments and was effective in patients who were less than fully ambulatory and in those who had lost weight. 5-Fluorouracil, Adriamycin, and mitomycin C appear to be a likely combination to be considered in a surgical adjuvant program.

Adenocarcinoma↗
PubMed1982

Phase II evaluation of dibromodulcitol, ICRF-159, and maytansine for sarcomas.

Patients with objectively measurable soft tissue sarcomas, osteosarcomas, chondrosarcomas, and mesotheliomas were treated with dibromodulcitol (DBD) (180 mg/m2 p.o. days 1-10 q4 wks.). ICRF-159 (300 mg/m2 p.o. tid days 1-3 q4 wks), or maytansine (MAYT) (1.5 mg/m2 I.V. q3 wks.). Forty-five evaluable patients received DBD, 47 MAYT, and 37 ICRF-159. Only patients who had had their histopathologic diagnoses confirmed by a pathology reference panel were included in the final analysis. Two patients had objective partial responses: a patient with osteosarcoma who responded to DBD and a patient with fibrosarcoma who had a partial response of brief duration to ICRF-159. Approximately 70% of the patients treated with each drug were of ECOG performance status 0 or 1, and over half had moderate or worse toxicity. It seems unlikely that these drugs have significant therapeutic activity for common mesenchymal malignancies.

Adolescent↗
PubMed1978

Phase I trial of ICRF-159 in combination with 1.3 bis-(2-chloroethyl)-1-nitrosourea (MeCCNU).

Both ICRF-159 and methyl-CCNU are agents with antitumor activity against gastrointestinal carcinoma; hence the exploration of this combination for possible synergism. Results of the study involving 19 patients show that bone marrow toxicity is the limiting factor for this combination of drugs. Moreover, a dose of 130 mg/mg of MeCCNU with 800 mg/m2/day of ICRF is well tolerated.

Bone Marrow↗
PubMed1971

Empyema thoracis.

Explore the source record for details and available documents.

Adolescent↗
PubMedDate not supplied

Increased resectability of locally advanced pancreatic and periampullary carcinoma with neoadjuvant chemoradiotherapy.

A prospective neoadjuvant trial utilizing chemotherapy (CTX) and radiotherapy (XRT) prior to pancreatectomy was established to determine the feasibility of resection after aggressive pretreatment and its effect on survival. Fifteen patients with pancreatic cancer (14 head, 1 body) and 1 patient with duodenal cancer, (with paraaortic adenopathy), were subjected to combination treatment with infusional 5-FU, bolus injection of mitomycin-C, and XRT (4 patients were treated off the protocol). Patients were restaged 3 wk after XRT, and those deemed resectable underwent a pancreatic resection. Three patients did not undergo exploration after the neoadjuvant therapy, although two of these were deemed resectable by CT scan. The remaining 13 patients underwent exploration and 10 underwent resection. Three did not undergo resection because of extrapancreatic disease, although their primary tumors were resectable. One patient had no residual tumor in the specimen. The others had residual tumor with evidence of necrosis and hyalinization, but all margins were free of tumor. There were two perioperative deaths from sepsis. Of the remaining patients who underwent resection, one died of a myocardial infarction at 9 mo. One patient died with recurrent disease at 19 mo. The remaining patients are alive 40, 32, 11, 11, 10, and 4 mo since diagnosis and are currently free of disease. Aggressive neoadjuvant chemoradiotherapy can be performed safely, allows successful resection, and may yield long-term survival or curve.

Adenocarcinoma↗
PubMedDate not supplied

Phase III study of ICRF-159 versus 5-FU in the treatment of advanced metastatic colorectal carcinoma.

Thirty-seven previously untreated patients with advanced metastatic colorectal carcinoma were treated in a prospective randomized fashion with either ICRF-159 or 5-FU. The ICRF-159 was administered orally at a dose of 1 g/m2/day for 3 consecutive days every 3 weeks, and the 5-FU was given iv at a dose of 450 mg/m2/day for 5 days every 5 weeks. All patients were evaluated for response and toxic effects after two courses of treatment. All those who failed to meet the criteria for objective response with either a complete remission or a partial response received the other drug in a crossover fashion. Three of the 18 patients (16%) initially treated with 5-FU achieved a partial response while none of the 19 patients initially treated with ICRF-159 achieved a complete or partial response. Nine prior 5-FU-treated patients were crossed over to ICRF-159 and 14 prior ICRF-159-treated patients subsequently received 5-FU. No antitumor response was seen with the secondary agent in this study. The response rate for ICRF-159 (none of 19 patients) predicts that it is unlikely to produce a true response rate of greater than or equal to 20% with a rejection error of less than 5%, making it unsuitable as primary therapy for colon carcinoma. The toxicity of 5-FU was moderate and mainly gastrointestinal while the toxicity of ICRF-159 was severe and mainly hematologic.

Clinical Trials as Topic↗