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Biomedical subjects

M Al-Sarraf

Publications and source records attributed to M Al-Sarraf.

At least 37 records · Page 2Linked to original sources
PubMed1988

Radiation Therapy Oncology Group (RTOG) studies in head and neck cancer.

Since its foundation in 1971, the RTOG has conducted a successful clinical research program in head and neck mucosal squamous cell carcinoma with 22 treatment protocols and one registry study which combined have accumulated data on over 5,500 patients. The RTOG was the first multicenter group to evaluate neoadjuvant chemotherapy before definitive radiation with its methotrexate study. Although the study was negative, RTOG has since conducted five pilot or phase II studies of neoinduction or concurrent chemotherapy with radiation therapy in patients with inoperable tumors. The last study showed that radiation concurrent with cisplatinum was tolerable with a suggestion of increased antitumor effect. In patients with potentially resectable tumors, RTOG has completed a pilot study of combination chemotherapy administered either before or after the surgery with radiotherapy. Based upon its findings, the treatment sequence, surgery-chemotherapy-radiotherapy, was chosen as the experimental arm for a new phase III study. This study was subsequently adopted by the head and neck intergroup mechanism as its study (INT 0034/RTOG 8503). RTOG has investigated the optimal timing of radiotherapy with surgery. The 7303 study established that postoperative radiotherapy achieved significantly better locoregional control but not improved absolute survival. Approximately 30% of the patients on each arm failed to complete both modalities. Even when comparison is restricted to patients who completed both modalities, postoperative radiotherapy still produced the better locoregional control. Efforts to overcome the limitations imposed by tumor hypoxia through use of carbogen (95% O2 and 5% CO2) breathing or the radiosensitizer misonidazole during radiotherapy have been unsuccessful. In a phase I study, RTOG showed that 15 to 18 sessions of sensitized radiation can be safely delivered with the new radiosensitizer SR 2508 in contrast to only six such sessions with misonidazole. This promising radiosensitizer is now being tested in a phase III trial. RTOG has also investigated variations in fraction size, fraction number, and total radiation dose. In the 7102 study, split-course irradiation achieved equivalent antitumor results as compared to continuous daily irradiation but with less social alteration and cost to the patient. In the hyperfraction pilot study 7703, twice a day irradiation with 120 cGys up to 6,000 cGys proved to be tolerable.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1987

Improved response and survival to combined cisplatin and radiation in non-keratinizing squamous cell carcinomas of the head and neck. An RTOG study of 114 advanced stage tumors.

Effective treatment modalities for Stage III and IV squamous cell carcinomas (SCC) of the head and neck are limited and seldom result in long term survival. The improved results with cisplatin containing chemotherapy have been encouraging and represent an additional therapeutic modality for head and neck cancer. To estimate the effectiveness of concomitant radiation and cisplatin chemotherapy, the Radiation Therapy Oncology Group (RTOG) initiated a Phase II study for patients with advanced nonresectable SCC of the head and neck. In addition, the diagnostic biopsy specimens were collected. Two pathologists reviewed and scored the biopsy specimens for a number of histologic parameters, including degree of keratinization, nuclear pleomorphism, frequency of mitoses, inflammatory and stromal reaction, pattern of invasion and vascular involvement in order to identify potential prognostically important patient subgroups. A total of 114 patients were evaluated for complete clinical responses (CR). These were achieved in 76% for all head and neck sites (ALL), and in 72% of the patients excluding nasopharyngeal and sinus cancers (REST). Evaluation of histopathologic parameters through multivariate analysis identified the presence of keratin as the most significant in predicting CR. Non-keratinizing SCC had CRs of 98% (ALL), and 94% (REST), as compared with 64% and 67% in the patients with keratin producing neoplasms (P less than 0.001 and 0.05) respectively. Survival at 24 months was found to be improved in the non-keratinizing SCC (P = 0.002). Multivariate analysis also identified the frequency of mitoses as being important in predicting for CR in patients with keratin in the biopsy findings. Biopsy specimens from ALL patients with two or more mitotic figures per high-power microscopic field had 76% CRs, in comparison with 46% when none or one mitotic figure was observed (P = 0.02). In the restricted group of patients (REST), the CR was 77% in the high mitotic figure group as opposed to 45% in the lower rate group (P = 0.03). However, this significant difference in CR rates did not translate into improved survival for the high CR subset.

Adult↗
PubMed1987

Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer.

In a series of three consecutive pilot studies conducted between 1977 and 1982 at Wayne State University, Detroit, Michigan, 191 consecutive patients with previously untreated, locally advanced head and neck cancer were treated with cisplatin (CDDP), vincristine, and bleomycin or CDDP and 5-fluorouracil (5-FU) infusion before definite surgery or radiation. A 39% (75/191) rate of complete clinical responses was achieved. Thirty-two of the chemotherapy-induced complete responders underwent radical surgery. Thirteen had no histologic evidence of residual disease in the surgically resected specimen. The CDDP and 5-FU infusion combination achieved the highest histologic complete response rate. All histologically complete responders who had completed local radiation therapy are clinically free of disease at median follow-up of 36 months. Patients who achieved complete response both clinically and histologically had superior survival as compared to patients who achieved complete response clinically and were subsequently found to have residual tumor in their surgically resected specimen (P = 0.01). An analysis of the clinical and pathological pretreatment characteristics was performed to identify factors predictive of histologic complete response. Advanced nodal disease correlated inversely with the achievement of negative histology in the surgically resected specimen (P = 0.02). No other factors were significant in predicting response.

Adult↗
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

Induction chemotherapy in advanced head and neck cancer. A Radiation Therapy Oncology Group Study.

Cisplatin (cis-platinum, 100 mg/m2) and fluorouracil (1000 mg/m2/d), for 120 hours' infusion every three weeks for three courses, produced a 93% overall response rate and a 54% complete clinical response at the single-institution level. The same combination was tested in the Radiation Therapy Oncology Group to evaluate the effectiveness and feasibility of this combination. An overall response rate of 86% was obtained, with a 38% complete clinical response. Only 27 of 42 patients completed planned surgery. Compliance with chemotherapy and radiation therapy was substantially better. No additional morbidity after surgical resection or postoperative radiation therapy was identified as secondary to the induction chemotherapy. We conclude that the combination of cisplatin and fluorouracil infusion is effective, with high complete clinical response rate in patients with advanced, previously untreated head and neck carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed1987

Chemotherapeutic management of head and neck cancer.

The use of chemotherapy in patients with head and neck cancer is increasing. In patients with recurrent head and neck cancer, a large number of chemotherapeutic drugs have shown antitumor activity. These drugs are discussed, and factors which influence response rate and survival are examined. New agents and treatment, including specific agents for combination chemotherapy, are presented. There has been a search for new treatments or procedures in patients with previously untreated and locally advanced cancer of the head and neck. The results, including studies of combined modality therapy and chemotherapy after surgery, are discussed. Chemotherapy in tumor of the salivary glands is briefly discussed, followed by an examination of intra-arterial therapy.

Antineoplastic Agents↗
PubMed1987

Pilot study of combination 5-fluorouracil, cisdiamminedichloroplatinum II, and radiation therapy for grade III and IV astrocytomas.

Nineteen patients with biopsy-proven high-grade astrocytomas received as initial treatment whole-brain radiation and combination chemotherapy with 5-fluorouracil (5-FU), 1,000 mg/m2/24 h as a continuous infusion for 96 h, and bolus cisdiamminedichloroplatinum II (CDDP), 100 mg/m2. Chemotherapy cycles were repeated on day 21, then every 28 days until progression or completion of six cycles. All 19 patients completed one cycle of chemotherapy. Toxicity was moderate, with cytopenias, nausea, vomiting, diarrhea, stomatitis, and reversible azotemia. Survival ranged from 2 to 160+ weeks, with a median of 35 weeks. The survival of the pilot group was compared with historical controls treated with radiation plus 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU). Controls were similar in histology, age, performance score, and survival, without statistically significant differences. The combination of radiation therapy, continuous-infusion 5-FU, and bolus CDDP as described here for high-grade astrocytomas is moderately toxic and appears to offer no survival advantage compared with radiation therapy plus BCNU.

Adolescent↗
PubMed1987

5-Fluorouracil cardiotoxicity: left ventricular dysfunction and effect of coronary vasodilators.

Seven patients developed clinical features simulating myocardial ischemia less than 72 hours after 12 of 13 separate intravenous 5-fluorouracil administrations; 9 episodes were associated with chest pain, 3 with hypotension, 3 with ventricular tachycardia and 1 with cardiogenic shock. Left ventricular dysfunction was demonstrated by echocardiography in 5 separate episodes, 2 with interval improvement upon repeat echocardiograms. Pretreatment with nitrates and/or calcium channel blockers failed to prevent recurrence of cardiotoxicity during 5 of 6 repeat 5-fluorouracil administrations. Therapy with 5-fluorouracil is associated with cardiotoxicity simulating myocardial ischemia with left ventricular dysfunction. Pretreatment with coronary vasodilators may not prevent this phenomenon.

Aged↗
PubMed1986

Meningeal carcinomatosis in head and neck cancer. Report of six cases and review of the literature.

Head and neck cancer has rarely been reported to be a cause of meningeal carcinomatosis. These tumors are known more for their local invasiveness rather than distant metastasis. This would appear to preclude meningeal involvement, but close proximity to multiple cranial nerves may provide an access to the meninges. Six cases of head and neck cancer with meningeal invasion are presented. All six cases had malignant cells in their cerebrospinal fluid. Three cases had malignant cells recovered from a ventricular specimen after lumbar punctures were negative. The most common clinical finding on presentation was cranial nerve involvement. The optic nerve was involved most often with nerves VI and V the next most frequent. Headache was present in four patients and seizures occurred in two. No patient had meningismus. Our current treatment plan involves insertion of an Ommaya Reservoir and intraventricular methotrexate. Only patients whose primary head and neck tumor shows a response to systemic therapy undergo Ommaya placement. Meningeal carcinomatosis in head and neck cancer may be more prevalent than previously thought and the likely mechanism is via direct extension rather than hematogenous spread.

Adult↗
PubMed1986

The activity of a single-agent 5-fluorouracil infusion in advanced and recurrent head and neck cancer.

Although chemotherapy regimens using cisplatin (CDDP) and 5-fluorouracil (5-FU) infusion have shown significant activity in advanced and recurrent head and neck cancer, their use requires normal renal function. The use of 5-FU infusion alone has not been evaluated in these tumors. Retrospective analysis revealed 11 patients who received 5-FU infusion alone because of poor renal function: 7 patients with recurrent disease who were previously treated with surgery and/or radiation therapy and 4 patients who received 5-FU as preoperative induction therapy for advanced disease were treated. The infusion dose consisted of 1000 mg/M2/24 hours for 96 hours for patients with previous radiation and 120-hour infusions for patients without previous radiation. The courses were repeated at 3-week intervals. Eight of 11 (72%) demonstrated a response (1 complete response [CR] and 7 partial responses [PRs]. Responses occurred in 4 of 4 (all PRs) patients with previously untreated epidermoid cancer, 1 patient with recurrent adenocystic cancer, and 3 of 6 patients with recurrent epidermoid cancer not previously treated with chemotherapy. Three patients, with no prior systemic or local therapy, who were clinical partial responders to 5-FU infusion went on to surgery and radiotherapy. Their responses were maintained for 18, 14, and 46+ months, respectively. The predominant toxicities were stomatitis (6/11, 55%) and leukopenia (2/11 patients). In this retrospective analysis, 5-FU infusion alone demonstrated good activity in head and neck cancer with tolerable toxicity. Since the number of patients is small and were selected on the basis of renal function, prospective evaluation is essential.

Aged↗
PubMed1986

The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy.

The response to initial treatment with cisplatin-containing combination chemotherapy as well as survival, were correlated with tumor differentiation (well, moderate or poorly differentiated) in 164 patients with advanced, untreated squamous cell carcinoma of the head and neck. Thirty-three percent of the tumors were graded as poorly differentiated, 59% moderately differentiated, and 8% were well differentiated. The overall clinical response rates were nearly equal for the three grades of differentiation: 79% for well differentiated, 86% for moderately differentiated, and 89% for poorly differentiated. The complete response rate was somewhat higher for poorly differentiated tumors: 46% as compared to 32% and 29% for moderately and well differentiated respectively, but the differences were not statistically significant. The median survival for each morphologic group was 22, 16, and 12 months for well differentiated, moderately differentiated and poorly differentiated tumor, respectively (P = 0.097). For patients achieving a complete clinical response to chemotherapy, there was a difference in survival when stratified according to degree of histologic differentiation. Patients who were complete responders and had well or moderately differentiated tumors attained 75% and 38% survival at 36 months, respectively, versus 19% for patients with complete response and poorly differentiated tumors (P = 0.064). The degree of differentiation of previously untreated squamous cell cancers of the head and neck does not conclusively predict tumor response to combination chemotherapy, but may reflect differences in natural history. Survival is improved in patients with differentiated tumors as compared to those with poorly differentiated tumors. Morphologic grading in patients achieving a complete response reveals a decrease in survival for patients with poorly differentiated 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↗
PubMed1986

Phase II clinical evaluation of AZQ in renal cell carcinoma.

Twenty-two patients with advanced measurable renal cell carcinoma were treated with AZQ 20 mg/m2 weekly for 4 weeks, followed by a 2-week rest. No complete or partial responses were observed among 15 fully evaluable patients. Stabilization was observed in eight individuals (range 8-27 weeks with a median of 12.5 weeks). Toxicity was primarily reversible myelosuppression. We conclude that AZQ administered at this dose and schedule has no significant activity against advanced renal cell carcinoma.

Adenocarcinoma↗
PubMed1986

Adjuvant chemotherapy with adriamycin, cytoxan, and cis-platinum in high-grade carcinoma of the prostate treated with definitive radiotherapy (RTOG pilot 81-12).

In a phase I-II trial, a regimen of Adriamycin, Cytoxan, and cis-Platinum has been tested as an adjuvant to definitive radiotherapy in patients with high-grade (Gleason score 8-10) locally advanced carcinoma of the prostate limited to the pelvis. The patients had no evidence of distant disease, were in good general condition, and had satisfactory cardiac, hepatic, and renal function. Radiation therapy consisted of 4,320-4,500 rad in 23-25 fractions to the pelvis followed by a boost to the prostate to a total of 6,480-7,020 rad in 36-39 treatments. Chemotherapy was scheduled to start 4 weeks after completion of radiotherapy and consisted of 300 mg/m2 of Cyclophosphamide, 30 mg/m2 of Adriamycin, and 50 mg/m2 of cis-Platinum cycles given at 4-week intervals. The primary aim of the study was evaluation of toxicity of the combined regimen. Nine patients were evaluable. No adverse effects of chemotherapy on the incidence and severity of radiation-related toxicity in the pelvis have been observed. Myelosuppression has been significant and has prevented delivery of full doses of chemotherapy. Although planned, no dose escalation was possible. Further reduction of dosage was necessitated in 67% of the patients. Delays in the delivery of chemotherapy were necessary in four patients; the delays ranged from 1 to 14 weeks. Although the regimen had been reported to produce a high rate of response in disseminated disease and has not been associated with an increased incidence of radiation-chemotherapy toxicity in the irradiated pelvis, it does not appear suitable for further testing in an adjuvant setup in patients treated with definitive radiotherapy.

Aged↗
PubMed1986

High-dose ketoconazole therapy in patients with metastatic prostate cancer.

High-dose ketoconazole, 400 mg orally every 8 h, was administered in two groups of patients with metastatic prostate cancer. Group A consisted of 10 patients who had not undergone orchiectomy and Group B, eight patients who had orchiectomy prior to the study. Significant declines in testosterone, androstenedione, and dehydroepiandrosterone levels, reciprocal elevation of the gonadotropin levels (FSH and LH), and a persistent fall in serum acid phosphatase levels were observed in Group A patients. Three Group A patients achieved a partial objective remission (duration 9, 41+, and 69 weeks); four patients, stabilization of their disease for a median of 33.5 weeks (range 16-40+ weeks); and two progressed (The National Prostatic Cancer Project Criteria). Stable disease in two Group B patients (7 and 20 weeks) and progression in four patients were observed. Gastrointestinal irritation was the main toxicity and was similar in both groups. Two Group A patients developed symptomatology consistent with adrenal insufficiency. Ketoconazole can suppress androgen production and has a beneficial role in the hormonal therapy of patients with prostate cancer who have not undergone orchiectomy.

Adenocarcinoma↗
PubMed1986

Randomized comparisons of radiotherapy and carmustine versus procarbazine versus dacarbazine for the treatment of malignant gliomas following surgery: a Southwest Oncology Group Study.

Between 1977 and 1981, the Southwest Oncology Group entered 278 patients on a randomized study (SWOG 7703) to compare the effect of three different chemotherapeutic agents given in combination with radiotherapy (6000 rads over 7 weeks) following surgery for malignant gliomas. The chemotherapy regimens were: carmustine (BCNU)--80 mg/m2 iv daily X 3 every 6 weeks; procarbazine (PCB)--100 mg/m2 orally; or dacarbazine (DTIC)--175 mg/m2 iv daily X 5 every 4 weeks. Patients were stratified according to age, and degree of resection, with no differences identified between groups. The response rates (complete plus partial) for BCNU and DTIC were significantly better than for PCB [BCNU, 39%; PCB, 13%; and DTIC, 38% (P less than 0.01)]. The response duration and survival were somewhat better in patients treated with BCNU and DTIC, but compared to patients treated with PCB, the difference was not statistically significant. Median survival times were: BCNU, 45 weeks; PCB, 31 weeks; and DTIC, 49 weeks (P greater than 0.3). There were six toxic deaths with BCNU and four with PCB, most of which were due to infection associated with leukopenia. The high toxicity and minimal benefit of chemotherapy added to radiotherapy compared to historical results with radiotherapy alone suggest that combined treatment may not be indicated for some patients.

Brain Neoplasms↗