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P F Engstrom

Publications and source records attributed to P F Engstrom.

At least 37 records · Page 2Linked to original sources
PubMed1995

Results of combined modality therapy for patients with anal cancer (E7283). An Eastern Cooperative Oncology Group study.

BACKGROUND: This prospective study assessed combined modality therapy of patients with International Union Against Cancer classification T1-4 N0 M0 anal cancer. METHODS: Protocol therapy consisted of a dose of 4000 cGy to the pelvis, anus, and perineum, followed by a 1000-1300 cGy boost. Infusions of 5-fluorouracil and mitomycin-C were administered when radiation therapy began. A second infusion of 5-fluorouracil was administered 28 days later. Biopsy was performed 6-8 weeks after completion of treatment. Positive biopsy findings resulted in abdominal-perineal resection. RESULTS: Survival at 7 years for 50 eligible patients was 58%. White patients and those with favorable performance status had significantly better survival. Of the 46 patients evaluable for response, 34 had a complete response, 11 had a partial response, and 1 had no response. Seven-year survival for partial responders was 53%. Freedom from locoregional progression was 80% at 7 years. CONCLUSION: Treatment with a combination of chemotherapy and radiation therapy is effective for patients with anal cancer. The investigation of methods of improving therapy is warranted.

Adult↗
PubMed1995

Glutathione S-transferase activity and glutathione S-transferase mu expression in subjects with risk for colorectal cancer.

The glutathione S-transferases (alpha, mu, and pi), a family of Phase II detoxication enzymes, play a critical role in protecting the colon mucosa by catalyzing the conjugation of dietary carcinogens with glutathione. We investigated the efficacy of using the glutathione S-transferase (GST) activity of blood lymphocytes and GST-mu expression as biomarkers of risk for colorectal cancer. GST activity was measured in the blood lymphocytes of control individuals (n = 67) and in the blood lymphocytes (n = 60) and colon tissue (n = 34) of individuals at increased risk for colon cancer. Total GST activity was determined spectrophotometrically with the use of 1-chloro-2,4-dinitrobenzene as a substrate. The ability to express the um subclass of GST was determined with the use of an ELISA. Although interindividual variability in the GST activity of blood lymphocytes was greater than 8-fold (range, 16.7-146.8 nmol/min/mg), the GST activity of blood lymphocytes and colon tissue within an individual was constant over time and was unrelated to sex, age, or race. The GST activity of blood lymphocytes from high-risk individuals was significantly lower than that of blood lymphocytes from control individuals (P < or = 0.004). No association was observed between the frequency of GST-mu phenotype and risk for colorectal cancer. Blood lymphocytes from high-risk individuals unable to express GST-mu had lower levels of GST activity than did those from control subjects with the GST-mu null phenotype; however, this difference was significant in male subjects only (P < or = 0.006). Analysis of paired samples of blood lymphocytes and colon tissue indicated a strong correlation between the GST activity of the two tissue types (Spearman's rank correlation, r = 0.87; P < or = 0.0001). The GST activity of blood lymphocytes may be used to identify high-risk individuals with decreased protection from this Phase II detoxication enzyme who may benefit from clinical trials evaluating GST modulators as chemopreventive agents for colorectal cancer. The GST activity of blood lymphocytes may also be used in colorectal cancer chemoprevention trials to monitor the responsiveness of colon tissue to regimens that modify Phase II detoxication enzymes.

Adult↗
PubMed1995

Management of adenocarcinoma of the esophagus with chemoradiation alone or chemoradiation followed by esophagectomy: results of sequential nonrandomized phase II studies.

PURPOSE: The incidence of adenocarcinoma of the esophagus is increasing, but the optimal treatment for this disease is unknown. We evaluated the efficacy of chemoradiation and chemoradiation followed by esophagectomy as treatment for adenocarcinoma of the esophagus in sequential prospective nonrandomized phase II studies. METHODS AND MATERIALS: Between May 1981 and June 1992, all previously untreated patients (N = 35) with potentially resectable adenocarcinoma of the esophagus (clinical Stage I or II) were treated with curative intent in sequential prospective Phase II studies. From May 1981 to August 1987, 11 patients (median age 66) were treated with concurrent chemotherapy [mitomycin C, and 5-fluorouracil (5-FU)] and radiotherapy to a median dose of 60 Gy (CRT group). From September 1987 to June 1992, 24 patients (median age 65) were treated with the same regimen of chemoradiation followed by planned esophagectomy (CRT+PE group). Of these, 12 patients (median age 62) actually underwent esophagectomy (CRT+E subgroup). RESULTS: The median overall survival was 19 months for the CRT group and 15 months for the CRT+PE group. For the CRT+E subgroup, the median overall survival was 33 months. The 3-year actuarial overall survival for the CRT and the CRT+PE groups were 36 and 28% (p = 0.949). The subset of patients treated with chemoradiation followed by esophagectomy had a 3-year actuarial overall survival of 33% (p = 0.274). The 3-year actuarial freedom from local failure rates were similar: 62% in the CRT group vs. 58% in the CRT+PE group. Of the 12 patients who underwent esophagectomy (CRT+E group), 9 (75%) were free of local failure. Four of 12 (33%) patients had no pathologic evidence of malignancy in their surgical specimen. Six of 11 patients (55%) in the CRT group were free of local failure at the time of analysis. Two of five patients in this group who had local recurrence at 2 and 10 months underwent surgical salvage with subsequent survivals of 20 and 100 months, respectively. Treatment-related mortality was 0 out of 11 in the CRT group and 2 out of 24 in the CRT+PE group. Dysphagia relief was similar in the CRT group vs. the CRT+E subgroup; however, a greater percentage of patients treated with chemoradiation alone had normal long-term swallowing function when compared to those patients also undergoing esophagectomy (100% vs. 73%). CONCLUSION: High-dose chemoradiation alone appears to provide similar survival and relief of dysphagia compared with high-dose chemoradiation followed by esophagectomy for patients with potentially resectable esophageal adenocarcinoma. Local failure may be higher in patients undergoing chemoradiation compared to chemoradiation followed by esophagectomy, but surgical salvage is possible, thus providing similar overall local control. However, because of the small number of patients in each group, these treatment modalities need to be further evaluated in a prospective randomized Phase III study.

Adenocarcinoma↗
PubMed1995

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis.

PURPOSE: To determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligibility required measurable disease (stage IV or stage IIIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count > or = 2,000/microL, platelet count > or = 100,000/microL serum creatinine concentration < or = 1.5 mg/dL, and bilirubin level < or = 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m2/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUC) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m2 per cycle to a maximum of 215 mg/m2. Treatment was repeated at 3-week intervals for six cycles. RESULTS: From June 1993 through February 1994, 54 patients were enrolled; 53 are assessable for toxicity and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had adenocarcinoma, and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 patients (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 patients (37%). Myelosuppression was the principal toxicity; grade 3 or 4 granulocytopenia occurred in 57% of patients after the first cycle, but decreased to 35% during the second cycle after introduction of G-CSF and consistently remained < or = 22% during subsequent cycles. Seven episodes of neutropenic fever occurred, all during the first cycle. Grade 3 or 4 thrombocytopenia and anemia occurred in 47% and 33% of patients, respectively. Eight patients (15%) required platelet transfusions and 16 (30%) required packed RBC support. Neuropathy, myalgias/arthralgias, and thrombocytopenia, although generally mild, were cumulative. The paclitaxel dose was boosted to 215 mg/m2 in > or = 70% of patients who received three or more cycles. At an AUC of 7.5, the median first-cycle carboplatin dose was 424 mg/m2 (range, 273 to 709 mg/m2). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%. CONCLUSION: The paclitaxel-carboplatin combination is active in advanced NSCLC and may enhance survival; it merits further investigation in phase III trials.

Adult↗
PubMed1995

Paclitaxel by 24- or 1-hour infusion n combination with carboplatin in advanced non-small cell lung cancer: the Fox Chase Cancer Center experience.

A phase II trial of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin included 54 chemotherapy-naive patients with advanced non-small cell lung cancer. Eligibility mandated Eastern Cooperative Oncology Group performance status of 0 or 1 and adequate hematologic, renal, and hepatic function. Paclitaxel 135 mg/m2 over 24 hours preceded carboplatin dosed to an area under the concentration-time curve of 7.5. Six planned courses were given every 3 weeks. Granulocyte colony-stimulating factor was introduced during the second and subsequent cycles, and paclitaxel increased 40 mg/m2/cycle (maximum, 215 mg/m2) in patients with absolute neutrophil and platelet nadirs exceeding 500/microL and 50,000/microL, respectively. Grade 3 or 4 neutropenia, observed in 54% of patients during cycle 1, declined to 35% during cycle 2 and to 22% or less during cycles 3 through 6. Neuropathy, myalgias/arthralgias, and thrombocytopenia were mild but cumulative. In 53 evaluable patients, the objective response rate was 62%, with 9% complete remissions and a median response duration of 6 months (range, 1 to 19+ months). At median potential follow-up of 16 months, 9% of patients remain progression free (52+ to 80+ weeks). Median survival is 12.5 months; 1-year survival is 54%. Paclitaxel/carboplatin is highly active in advanced non-small cell lung cancer; granulocyte colony-stimulating factor abrogates neutropenia as the dose-limiting toxicity, but has no effect on the cumulative incidence of thrombocytopenia or treatment delays. One-hour paclitaxel infusion is minimally myelosuppressive, logistically easier, and less costly. A follow-up study combined paclitaxel (175 mg/m2) over 1 hour followed by carboplatin (area under the concentration-time curve, 7.5). In the absence of grade 4 myelosuppression, paclitaxel was increased 35 mg/m2/cycle (maximum, 280 mg/m2). Granulocyte colony-stimulating factor was implemented only after neutropenic fever or grade 4 neutropenia. Of 17 patients entered, 13 are evaluable for toxicity and seven for response. Four patients have sustained a partial response, two a minor response, and one stable disease. The incidence of grade 3 or 4 neutropenia, thrombocytopenia, and anemia in cycle 1 was 38%, 16%, and 0%, respectively, and 72%, 28%, and 28%, respectively, during cycle 2. Major nonhematologic toxicities include myalgias and arthralgias (54%) and fatigue and neuropathy (78%), the latter cumulative and progressive over successive cycles. Preliminary data suggest comparable activity for the 1- and 24 hour paclitaxel infusions in combination with carboplatin. The more severe neuropathy of the 1-hour paclitaxel/carboplatin combination may be related to the paclitaxel dosing schema (175 mg/m2 to as high as 280 mg/m2).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Cancer prevention and control priorities for the year 2000. A commentary.

It is time for the American Cancer Society and the nation to reevaluate the direction and impact of cancer prevention and control research. This article presents a new framework that integrates cancer control activities (fundamental research, intervention research, program delivery, and surveillance and monitoring) with knowledge synthesis and decision-making.

Forecasting↗
PubMed1994

Promoting mammography use through progressive interventions: is it effective?

This study evaluated interventions implemented with women in a health maintenance organization who had not utilized their annual free mammogram referral 45 days (step 2) and 95 days (step 3) after its mailing. The step 2 evaluation compared mammography utilization for women randomly assigned to receive a brief reminder letter or no reminder: 42% of the reminder group vs 28% of the control group obtained mammograms. The step 3 evaluation compared utilization for women randomly assigned to receive a second reminder, a letter suggesting a preventive office visit, or telephone counseling: 29% of those who received telephone counseling, 14% of those who received a letter, and 12% of those who received a second reminder obtained mammograms.

Aged↗
PubMed1994

Coordinate induction of glutathione S-transferase alpha, mu, and pi expression in murine liver after a single administration of oltipraz.

The antischistosomal agent oltipraz displays a unique ability to inhibit chemically induced carcinogenesis in a variety of animal models. Its apparent lack of carcinogen specificity and low toxicity make it an attractive candidate for further development as a chemopreventive agent. The mechanism by which oltipraz affords cellular protection is thought to involve the modulation of phase II detoxication enzymes. The present study examines the regulation of each class of glutathione S-transferase (EC 2.5.1.18) in mice after a single oral administration of oltipraz. Glutathione S-transferase activity in the liver increased in a dose-dependent manner after drug exposure. Oltipraz administration (1 g/kg, by gavage) elevated glutathione S-transferase activity to a maximum (4.5-fold) on day 4 after treatment. Western blot analyses demonstrated the induction of all three classes of glutathione S-transferase (alpha, mu, and pi) by oltipraz. Our murine studies suggest that the chemopreventive activity of oltipraz may be due in part to its ability to elevate glutathione S-transferase-mu activity. Consistent with this possibility, associations between the glutathione S-transferase-mu-null phenotype and increased risk for lung, larynx, and bladder cancer have been recently demonstrated in humans. Coordinate elevations in enzymatic activity were preceded by significant elevations in glutathione S-transferase alpha, mu, and pi RNA on day 2 after treatment. Although nuclear run-on assays confirmed the transcriptional induction of all three classes, the maintenance of elevations in enzymatic activity after RNA levels returned to base-line suggests that additional mechanisms are required to regulate glutathione S-transferase expression. Preclinical findings are presented that characterize the response of each class of glutathione S-transferase to oltipraz exposure and support the use of these enzymes as intermediate markers of the chemopreventive activity of oltipraz.

Animals↗
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

Academic detailing: a model for in-office CME.

The National Cancer Institute (NCI), in its goal to reduce cancer mortality by 50% by the year 2000, has placed a special emphasis on prevention and early detection, especially in underserved populations. Check-Up On Health is a community based health education program being carried out by Fox Chase Cancer Center in three inner city Philadelphia neighborhoods, to improve the provision of appropriate cancer screening and prevention services to older, blue-collar adults by their primary care physicians. Primary care physicians in the chosen neighborhoods were targeted to receive a brief cancer prevention educational message delivered by project staff and patterned on the model of drug detailing developed by the pharmaceutical industry. This study represents an attempt to evaluate the feasibility and acceptability of such an approach aimed at improving cancer prevention promotion in the health care system. Primary care physicians were identified by community residents who attended one of 67 Check-Up On Health education presentations about cancer prevention at churches, social clubs, and senior-citizen centers within the targeted neighborhoods. An attempt was then made by project staff to visit each identified physician in his/her office or clinic, during office hours, both to conduct a brief survey and to deliver an educational message about either cancer screening guidelines or counseling for smoking cessation. The physicians were also provided with educational materials for themselves as well as their patients. Twelve months after the visit, a follow-up phone call to the physicians assessed the impact of the visit and solicited suggestions for future outreach efforts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Surveillance for colorectal neoplasia: is patient adherence following treatment a problem?

This study was conducted in order to assess prospective adherence to surveillance colonoscopy and fecal occult blood testing (FOBT) at 1 year following treatment for an index lesion among colorectal cancer and polyp patients. The investigation was carried out in cooperation with two gastroenterology and two surgical practices in Philadelphia and surrounding communities. Subjects in this study were patients who were treated for colorectal cancer (N = 9) or polyps (N = 169) and were recommended to undergo surveillance colonoscopy at 12 months following treatment. Overall, 96 (54%) subjects underwent surveillance colonoscopy. Of the 178 subjects included in the study, 52 (29%) were willing to participate in an assessment of FOBT sensitivity in surveillance. Of the 52 subjects who were mailed an FOBT packet, 24 (46%) actually returned specimen. Of the 24 patients who returned FOBTs, 17 (71%) also underwent colonoscopy, whereas only 10 (36%) of 26 patients who did not do FOBTs underwent colonoscopy. These findings indicate that adherence to surveillance is low, and that adherence to FOBT may be a marker for adherence to colonoscopy.

Adenomatous Polyps↗
PubMed1992

Phase II trial of PALA in combination with 5-fluorouracil in advanced pancreatic cancer.

Phosphonacetyl-L-aspartate (PALA), in inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m2 on day 1, followed 24 h later by 2,600 mg/m2 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.

Adenocarcinoma↗
PubMed1991

Phase I/pharmacokinetic reevaluation of thioTEPA.

Because the initial evaluation of N,N',N''-triethylenethiophosphoramide (thioTEPA) preceded the standardized approach to the Phase I trials, uncertainty surrounds the recommended dose. Since it has recently been demonstrated that an almost 100-fold increase in dose can be administered in bone marrow transplant regimens, we conducted a Phase I reevaluation of thioTEPA. ThioTEPA was administered i.v. in 50 ml 5% dextrose in water over 10 min. Twenty-seven patients were entered at doses ranging from 30 to 75 mg/m2. The major toxic effect was myelosuppression; thrombocytopenia greater than or equal to grade 3 occurred in four of seven patients, and leukopenia greater than or equal to grade 3 in two of seven patients at 75 mg/m2. Among eight patients at 65 mg/m2 only two had greater than or equal to grade 3 myelosuppression making this the recommended new phase II dose for the majority of patients. Moderate (grade 2) easily controlled nausea and vomiting was the only other major side effect. There was no alopecia or mucosal or neurological toxicity. Three partial remissions were observed among nine previously treated ovarian cancer patients. Plasma concentrations of thioTEPA and its major active metabolite triethylenephosphoramide (TEPA) were measured by gas chromatography. The half-life of thioTEPA ranged from 51.6 to 211.8 min, and its pharmacokinetics was dose dependent; total body thioTEPA clearance decreased with increasing dose. The half-life of TEPA was considerably longer than that of the parent compound (3.0 to 21.1 h); as a result, the area under the plasma concentration-time curve (AUC) of TEPA was severalfold greater than that of the parent compound. The ratio of TEPA AUC to thioTEPA AUC decreased with increasing dose, suggesting that formation of TEPA is a saturable step in elimination. The AUC and total body clearance of thioTEPA, but not of TEPA, were closely correlated with neutrophil but not platelet toxicity.

Dose-Response Relationship, Drug↗
PubMed1991

Psychological and behavioral implications of abnormal mammograms.

OBJECTIVE: To evaluate women's psychological responses to abnormal mammograms and the effect on mammography adherence. To identify psychological responses and other factors that predict mammography adherence in women with normal or abnormal mammograms. DESIGN: Survey study with prospective analysis of factors associated with mammography adherence. SETTING: Health Maintenance Organization of Pennsylvania and New Jersey (HMO PA/NJ). PATIENTS: Study patients, members of HMO PA/NJ who were 50 years of age or older, and who had had mammography done 3 months earlier, included women with normal mammograms (n = 121), women with low-suspicion mammograms (n = 119), and women with high-suspicion mammograms (n = 68), but not women with breast cancer. MEASUREMENTS: Psychological responses 3 months after mammography and adherence to subsequent annual mammography were assessed. MAIN RESULTS: Women with high-suspicion mammograms had substantial mammography-related anxiety (47%) and worries about breast cancer (41%). Such worries affected the moods (26%) and daily functioning (17%) of these women, despite diagnostic evaluation excluding malignancy. For each variable, a consistent trend (P greater than 0.05) was seen with degree of mammogram abnormality. Sixty-eight percent of women with normal results, 78% of women with low-suspicion results, and 74% of women with high-suspicion results obtained their subsequent annual mammograms (P greater than 0.05). The number of previous mammograms (odds ratio, 3.2; 95% CI, 1.6 to 6.2) and the effect of the previous results on concerns about breast cancer (odds ratio, 0.5; CI, 0.2 to 1.0) were independent predictors of adherence in logistic regression analyses (P less than 0.05). CONCLUSIONS: A substantial proportion of women with suspicious mammograms have psychological difficulties, even after learning that they do not have cancer. Such sequelae do not appear to interfere with subsequent adherence.

Aged↗
PubMed1991

Specific compliance issues in an antiestrogen trial of women at risk for breast cancer.

Compliance is of enormous consequence to the study aims and to the reliability of results that emerge from a long-term antiestrogen chemoprevention trial. It is important that such a trial utilize a committed population who receive adequate study materials to inform them of the aims of the trial and to motivate continued compliance. A run-in period on a placebo should precede actual randomization. A simple dosing schedule of once per day, or at the most twice per day, is essential for program success. Subjects need to be contacted frequently and may need an incentive to comply. The assessment of compliance requires careful monitoring and follow-up of subjects on scheduled visits and completion of scheduled questionnaires. Medication use self-report and pill counts should be used and the collection of periodic blood follicle-stimulating hormone samples should be a part of the study although only a small sample of this sera plasma actually will be utilized for determining compliance. These compliance-enhancing strategies can help to ensure the integrity of this important trial.

Biomarkers↗
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↗
PubMed1991

Phase II study of aminothiadiazole in advanced squamous cell carcinoma of the esophagus.

Twenty-three patients with advanced inoperable squamous cell carcinoma of the esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus allopurinol daily in a phase II cooperative group trial. No patients responded to treatment; 17 patients progressed, three showed stable disease, and three were unevaluable. There were no life-threatening hematologic or metabolic toxicities. The median survival from study entry was 5 months. A-TD is not active in advanced squamous cell carcinoma of the esophagus.

Adult↗