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J F Ensley

Publications and source records attributed to J F Ensley.

51 records · Page 3Linked to original sources
PubMed1989

The correlation of specific variables of tumor differentiation with response rate and survival in patients with advanced head and neck cancer treated with induction chemotherapy.

The authors have reported previously that conventionally defined grades of tumor morphology do not correlate with tumor response or survival in advanced squamous cell cancers of the head and neck (SCCHN) treated with cisplatinum combination induction therapy. This lack of correlation may be the result of the imprecision and subjectiveness of the conventional grade determination. To examine this possibility, response and survival were correlated with individual parameters of morphologic differentiation in 136 patients with advanced, untreated SCCHN. A multi-variable analysis of degree of keratinization, number of mitotic figures per high powered field, degree of nuclear differentiation, presence of vascular invasion, intensity of inflammatory response, and invasion pattern of the cancer was performed. The grade of each variable was weighted by assigning a score from 1 to 4, with 1 representing the most differentiated and 4 the least. The cumulative score of each specimen was tallied and assigned to one of three groups, less than 12, 12 to 18, and greater than 18, analogous to the conventional grades of well, moderately, and poorly differentiated, respectively. No correlation between the grade of individual morphologic variables and response to chemotherapy was demonstrated, or between tumor response and cumulative score groups. There was no correlation of the grade of individual morphologic variables or cumulative score groups with survival. Only the survival of patients achieving a complete response to chemotherapy was correlated with the cumulative score groups: 2-year survivals of 84%, 70%, and 46% for less than 12, 12 to 18, and greater than 18, respectively. Multi-parameter analysis of individual features of tumor differentiation is not superior to conventional morphologic analysis in predicting response to chemotherapy or survival in patients with advanced SCCHN.

Adult↗
PubMed1989

Cellular DNA content parameters in untreated and recurrent squamous cell cancers of the head and neck.

The presence and degree of DNA aneuploidy as measured by the DNA index (DI) and the S phase fraction (SPF) were determined by flow cytometry in 294 specimens from 237 patients with untreated and recurrent squamous cell carcinomas of the head and neck (SCCHN). A descriptive analysis was performed in which the specimen DNA parameters were correlated with stage, size of primary, degree of lymph node involvement, morphological grade, and treatment status of the corresponding patients. Approximately 70% of the previously untreated specimens contained DNA aneuploid populations (DI greater than 1.10) and three quarters had SPF that were above 15%. There was a strong, direct association between DI and SPF (P less than 0.001). There was no correlation of the presence or degree of DNA aneuploidy with the stage of the tumor or the size of the primary or conventional morphological grade of the tumor. Specimens from patients with recurrent tumors and untreated patients with N3 lymph nodes had significantly lower rates of DNA aneuploidy and mean DI. Serial determinations of DNA aneuploidy in patients with SCCHN undergoing cytotoxic therapy are ongoing and may prove useful in the identification and understanding of resistance and response in this tumor.

Adult↗
PubMed1989

The clinical syndrome of 5-fluorouracil cardiotoxicity.

5-fluorouracil (FUra) is one of the most frequently used drugs in cancer treatment, particularly in combination with other agents. Its activity when administered as an infusion rather than a bolus has led to a renewed and increased use. A cardiotoxicity that mimics ischemia has been associated with the administration of FUra in cancer patients. This cardiotoxicity may manifest itself as: (a) dysrythmias with and without cardiorespiratory symptoms (b) ECG changes with and without cardiorespiratory symptoms (c) cardiorespiratory symptoms with and without ECG changes (d) acute myocardial infarct; symptoms and ECG changes (e) ventricular dysfunction (f) cardiogenic shock and (g) sudden death. Several case studies which illustrate the cardiotoxic sequelae that may be associated with the use of this drug are discussed. The incidence, contributing factors, risk factors and mechanisms underlying this phenomenon are undetermined. No appropriate recommendations for monitoring patients or for predicting those patients that will develop such toxicity while receiving FUra can be made at present. Prospective studies to determine the true incidence, spectrum and mechanisms causing this syndrome are ongoing and required for its understanding and prevention.

Adult↗
PubMed1988

Chemotherapy for paranasal sinus carcinoma. A 10-year experience at Wayne State University.

The role of chemotherapy in the management of patients with cancer of the paranasal sinus has not been defined. An analysis of 24 evaluable patients treated with chemotherapy as part of their overall therapy was performed. There were 16 male patients and eight female patients. Sixteen patients were previously untreated and eight had recurrent disease after surgery and/or radiotherapy. Six of the previously untreated patients had metastatic disease on presentation (four central nervous system (CNS) and two lung), and four recurrent patients had CNS involvement. The majority of patients (78%) had squamous cell carcinoma. The chemotherapy regimens included cisplatin (CDDP), vincristine (VCR), and bleomycin (COB), 5-fluorouracil (5-FU) infusion and CDDP, or 5-FU/CDDP and methotrexate (MTX). All patients had computed tomography (CT) measurable disease. Previously untreated patients underwent surgery and/or radiotherapy postchemotherapy. The overall response rate to chemotherapy for previously untreated patients was 82% (complete response [CR] 44%, partial response [PR] 38%) and for recurrent patients 88% (CR 38%, PR 50%). Predominant toxicities were nausea, vomiting, myelosuppression, mucositis, and renal impairment. The median survival of the previously untreated patients, based on response to chemotherapy, was as follows: CR 21+ months (range, 10+ to 81 months), PR 13.5 months (range, 2 to 21 months), and no response (NR) 3 months (range, 1 to 7 months). The median survival of patients with recurrent disease was as follows: CR 16 months, PR 13.5 months, and NR 5 months. We conclude that patients with paranasal cancers are responsive to CDDP-containing combinations. The role of adjuvant chemotherapy in previously untreated, locally advanced patients needs to be demonstrated by future randomized trials.

Adenocarcinoma↗
PubMed1988

Evaluation of high-dose cisplatin and 5-FU infusion as initial therapy in advanced head and neck cancer.

The combination of cisplatin and 5-fluorouracil (5-FU) infusion in head and neck cancer patients produces an overall response rate of 90% for advanced disease and 70% for recurrent disease. Whether or not escalating the platinum dose in combination with other agents, as has been done with refractory ovarian and testicular patients, would improve the response rates in patients with advanced head and neck cancer has not been evaluated. We undertook a study to determine the most efficacious dose of cisplatin that could be administered with 5-FU infusion in head and neck cancer patients. Eleven patients entered the study. Initial dose of cisplatin was 40 mg/m2 (in hypertonic saline) on days 1-5 plus 5-FU 1,000 mg/m2 on days 1-5 as a continuous infusion. Subsequent cisplatin doses were adjusted for the main toxicity, which was myelosuppression. The safest tolerable dose was 30 mg/m2 for 5 days. Overall response was 90% [45% complete response (CR) (5/11) plus 45% (5/11) partial response (PR)] which is comparable to that seen with cisplatin 100 mg/m2 and 5-FU in a 120-h infusion. Although patient numbers are small, there was no appreciable difference in response rate with higher dose cisplatin and there was a significant increase in serious toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study.

In patients who have locally advanced and inoperable head and neck cancer, the achievement of initial local control (complete response) of the disease with initial definitive treatment with radiotherapy (RT) with or without chemotherapy, is an important prognostic factor for overall survival. Cisplatin 100 mg/M2-intravenously (IV) with hydration and mannitol diuresis was given every 3 weeks for three doses concurrently with definitive radiotherapy (followed by salvage surgery [if possible] for persistent disease) was activated by the Radiation Therapy Oncology Group (RTOG) in 1981. One hundred thirty-four patients were initially registered and 124 were eligible and analyzed for this report. Eighty-two percent of the patients had Stage IV disease and greater than 50% of the primary sites were in oropharynx (39%), nasopharynx (22%), and oral cavity (18%). Eighty-seven percent of the patients are known to have finished the planned RT greater than 6450 cGy and 60% received three courses of cisplatin. Overall, 60% finished the planned combined treatment. Complete response to initial treatment occurred in 69% and an additional one patient (1%) was rendered disease-free after radical node dissection. Severe toxicities were as follows: leukopenia, 11%; anemia, 8%; nausea and vomiting, 6%; stomatitis, 31%; and renal, 6%. One toxic death occurred when a nephrotoxic antibiotic was administered at the same time. All patients were evaluated for total disease and survival regardless of compliance to the treatment or the cause of death. At 1 year, an estimated 51% of the patients had their disease totally controlled and an estimated 66% were alive. Incidence of initial complete response by various patient characteristics also were analyzed. The authors concluded that the combination of cisplatin and radiotherapy is an effective and safe treatment in patients with advanced head and neck cancer and needs to be tested against radiotherapy alone.

Adult↗
PubMed1987

Solid tumor preparation for flow cytometry using a standard murine model.

The application of flow cytometry (FCM) to solid human tumors has been hindered by the difficulty in producing high yield, viable, unaltered single cell suspensions. Carcinomas containing a high desmosomal content, such as well-differentiated squamous cell (SCC) cancers of the head and neck (H&N) region, are particularly difficult to prepare. The desire to employ FCM to study cellular DNA parameters of these tumors led to the use of a 3-methylcholanthrene induced murine SCC for the comparative testing of preparative techniques. Dissociation techniques, including mechanical, enucleation, chemical, single and combination enzymes methods, were comparatively tested. Of these, the combination enzyme treatment employing trypsin and collagenase produced the highest cell yields in the shortest time with the highest dye exclusion viability and the least expense. Several fixation systems including glutaraldehyde, paraformaldehyde, acetic acid, and ethanol were comparatively tested using percent of cell loss and quality of the DNA histograms produced as end points. Ethanol-water systems with added fetal calf serum provided minimal cell loss and high quality histograms which were stable for extended periods of time. A murine tumor, closely mimicking the histology of the human tumor of interest, may be used as a model for the determination of optimum techniques of solid tumor preparation for flow cytometric analysis.

Animals↗
PubMed1987

Solid tumor preparation for clinical application of flow cytometry.

Intense interest in advanced squamous cell cancers of the head and neck (SCC of H&N) has resulted from the recent progress made in tumor responses with chemotherapy and radiotherapy. Unfortunately, the response patterns and clinical outcome of such patients are not adequately predicted on an individual patient basis using clinical parameters or conventional morphology. The study of flow cytometrically determined cellular parameters in such tumors is therefore of interest, but is hindered by inadequate tumor preparative technology. The previous article (10) in this journal describes the use of a murine SCC tumor, LC12, which was employed for comparative testing and determination of optimum techniques of preparation for this tumor. This report describes the application of these techniques to 144 specimens of human SCC of H&N. The mean total yield for these specimens is 7.4 X 10(7) cells/g of tissue. The mean viable enzymatic yield (3.3 X 10(7) cells/g) was higher than the mean viable mechanical yield (2.0 X 10(7) cells/g) except when lymph nodes were the source of the specimen (5.4 X 10(7) cells/g). The mean dye exclusion viability from enzymatically dissociated specimens were above 90%. Significant aneuploidal subpopulation losses were evident in mechanically dissociated and enucleated specimens. 65% of the enzymatically dissociated specimens were successfully cultured with a mean cloning efficiency of 2.1 X 10(-3). Preparative techniques derived from comparative testing with a murine standard tumor have been successfully applied to 144 specimens of SCC of H&N with resultant high yields and excellent viability. Technical problems detected during the preliminary testing with LC12 were confirmed in the human tumors.

Adult↗
PubMed1986

Combined modality therapy utilizing a cisplatin combination for effective chemotherapy in patients with previously untreated head and neck cancer.

In patients with locally advanced head and neck cancer, the results of standard definitive treatments of surgery, radiotherapy, or both were disappointing. The local and regional recurrence rates were high, despite adequate surgical resection with negative margins and postoperative radiotherapy to all known or possible disease areas. Combination cisplatin chemotherapy given initially before definitive treatments produced a high overall antitumor response and up to 50 percent clinical complete response. Before answering the question of value of chemotherapy as part of the multimodality treatment, it is important to identify the safest and most form of chemotherapy. The degre of chemotherapy effectiveness is defined by the incidence of clinical and, most important, histologic complete response. To assess this effectiveness, chemotherapy was given before definitive treatments to patients with measurable disease. From our 10 year experience we have concluded that continuing the development of induction chemotherapy, including investigating the timing of such effective treatment and assessing the value of such therapy, is of the utmost importance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

A randomized trial of cisplatin (CACP) + 5-fluorouracil (5-FU) infusion and CACP + 5-FU bolus for recurrent and advanced squamous cell carcinoma of the head and neck.

One of the most active chemotherapeutic regimens for treatment of advanced and recurrent head and neck cancer is cisplatin (CACP) + 5-fluorouracil (5-FU) infusion with a response rate of 90% in advanced, previously untreated patients and 70% in patients with recurrent disease. Forty-four patients from two Wayne State University-affiliated hospitals were entered into a randomized trial of CACP (100 mg/m2) day 1 and 24-hour infusion of 5-FU (1000 mg/m2) days 1 through 4 versus CACP (100 mg/m2) day 1 and bolus 5-FU (600 mg/m2) day 1 and day 8. Thirty-eight patients were evaluable for three induction courses. Response for the infusion arm was 72% (4/18 complete response [CR] + 9/18 partial response [PR]). Response for the bolus arm was 20% (2/20 CR + 2/20 PR). The difference in response was statistically significant by chi-square analysis (P less than 0.01). Seventy percent of the patients on the bolus arm experienced leukopenia with several episodes of grades 3 and 4 leukopenia. In addition, 50% of the patients on the bolus arm experienced thrombocytopenia. Stomatitis was more frequent on the infusion arm but it was mild and reversible. The complete responders on either arm have a median survival of 120+ weeks; partial responders, 30 weeks. Cisplatin + 5-FU infusion produces a superior response as initial chemotherapy for three courses compared with CACP and 5-FU bolus.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck.

Induction chemotherapy, followed by surgery and/or radiotherapy was utilized in patients with advanced squamous cell carcinoma of the head and neck. During these trials, the authors observed that response to chemotherapy predicts further response to subsequent radiotherapy. This study was comprised of 57 patients with 60 separate neoplasms who demonstrated less than complete response (partial or no response) to initial treatment with a combination chemotherapy containing cisplatin. Subsequently radiotherapy, either 5000 rad preoperatively or 6600 rad as definitive therapy, was employed. Forty-one of the 42 tumors with initial partial response to chemotherapy also responded to radiotherapy (97.6%). Only one of the 18 tumors that initially failed to respond to chemotherapy subsequently responded to radiotherapy (5.5%). This observation suggests that patients with head and neck cancer sensitive to initial chemotherapy share parameters that are also radiation sensitive.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Proto-chemotherapy in advanced head and neck cancer.

Induction (proto) chemotherapy consisting of 3 courses of cisplatin and 120-hour 5-fluorouracil infusion was administered to 88 patients who had locally advanced, previously untreated head and neck cancer. The majority (81%) of these patients were classified as stage IV, and 17% had second primary carcinomas of the upper aerodigestive tract. An overall response rate of 94% was observed, with a 54% incidence of complete clinical response. The toxicity of the chemotherapy was judged acceptable, and no life-threatening or fatal drug-related side effects occurred. Twenty-four percent of the patients failed to comply with recommended standard treatment. In patients achieving a complete clinical response, 47% refused recommended surgery. Any response less than a complete clinical response to induction chemotherapy was not associated with any survival advantage. We conclude that future research efforts should be directed toward the identification of chemotherapeutic regimins that maximize the incidence of complete clinical response. In addition, any large-scale chemotherapy trial in patients with resectable disease should avoid the use of an induction sequence to minimize compliance problems with standard treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Evaluation of Tomudex in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group study.

A phase II trial of Tomudex (raltitrexed, ZD 1694), a new thymidylate synthase inhibitor, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This trial demonstrated that Tomudex was well tolerated in this patient population. Nausea and vomiting were minimal, and hematologic toxicities were relatively infrequent. Only one patient was withdrawn from the study due to toxicity (grade 4 diarrhea). One patient exsanguinated from a rent in the carotid artery in an area of tumor involvement, and was categorized as a grade 5 toxicity. Thus 25/27 patients were able to complete at least 2 cycles of treatment. Tomudex demonstrated a 3.7% response rate (95% CI 0.1-19%), with a median survival of 6 months in this highly resistant disease population. Tomudex is not considered active enough as monotherapy for further evaluation in this disease population.

Aged↗
PubMedDate not supplied

Feasibility trial of postoperative radiotherapy and cisplatin followed by three courses of 5-FU and cisplatin in patients with resected head and neck cancer: a Southwest Oncology Group study.

BACKGROUND: Appropriate adjuvant chemotherapy for resected head and neck cancer patients has yet to be defined. Multiple trials have noted trends toward improved disease-free survival and local control. The Southwest Oncology Group undertook a feasibility trial of postoperative cisplatin and radiotherapy followed by three cycles of cisplatin and 5-fluorouracil. METHODS: Patients with resected stage III or IV head and neck cancer received cisplatin, 100 mg/m2, on days 1, 22, and 43 of radiotherapy. This therapy was followed by three cycles of cisplatin, 100 mg/m2 or last tolerated dose, and 5-fluorouracil, 1000 mg/m2, on days 1 to 4 every 21 days. RESULTS: Seventy-two patients from 22 institutions were registered; 68 were evaluable. Sixty-eight patients received radiotherapy. Only 25 of 68 patients (36.7%) were able to complete all six cycles of chemotherapy. Forty-three of 68 patients (63%) completed all three cycles with radiotherapy. Toxicities were tolerable. One toxic death occurred. CONCLUSIONS: It is not feasible to deliver six cycles of chemotherapy postoperatively in the sequence described. Compliance issues need further exploration to define effective adjuvant chemotherapy for head and neck patients.

Adult↗