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M Al-Sarraf

Publications and source records attributed to M Al-Sarraf.

At least 19 recordsLinked to original sources
PubMed1991

5-year results of cisplatin and fluorouracil infusion in head and neck cancer.

As part of the developmental process for the Head and Neck Intergroup trial of adjuvant chemotherapy for advanced resectable head and neck carcinoma, in 1981 the Radiation Therapy Oncology Group, Philadelphia, Pa, conducted two nonrandomized pilot studies using chemotherapy consisting of three courses of cisplatin and fluorouracil infusion. Chemotherapy was administered prior to surgery in 42 patients (induction) and after surgery in an additional 29 patients (sequential). The populations were roughly comparable with respect to tumor site and stage. Twelve of the 42 patients in the induction group and seven of the 29 in the sequential group are alive and with no evidence of disease at the last reported follow-up. The median survival was 31 months in the sequential group vs 20 months in the induction group. Only two of the 26 patients with less than a complete clinical response following induction chemotherapy are still alive. Twenty-seven of the 42 patients who received induction chemotherapy did not undergo surgery as initially planned. Despite the lack of surgery, at 5 years the survival between the two groups was not significantly different (27% for the induction group vs 23% for the sequential group).

Adult↗
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

Metoclopramide versus metoclopramide and lorazepam. Superiority of combined therapy in the control of cisplatin-induced emesis.

Sixty-four patients treated with cisplatin-containing regimens were entered into a randomized, double-blinded study examining the antiemetic efficacy of metoclopramide with and without lorazepam for control of cisplatin-induced emesis. Metoclopramide was administered to all patients at 2 mg/kg, intravenously, 30 minutes before chemotherapy and 1.5, 3.5, and 5.5 hours posttreatment. Patients randomized to receive combined antiemetic therapy were administered lorazepam at 2 mg/m2 (maximum, 4 mg dose) intravenously, 30 minutes before chemotherapy. Those patients not receiving lorazepam were given normal saline placebo. Degree of nausea and number of vomiting episodes were recorded on a data flow sheet with a visual analogue scale. Drug toxicities were evaluated before each administered dose. Patients receiving both metoclopramide and lorazepam experienced significantly less vomiting episodes (P less than 0.05) and nausea (P less than 0.01) when compared to patients given metoclopramide alone. Forty-four percent of those receiving the combined therapy reported no nausea or vomiting episodes compared to only 22% receiving metoclopramide alone. Sedation was significantly more common in patients receiving lorazepam (88%) as opposed to patients receiving only metoclopramide (43%), P less than 0.01. Amnesia was seen in 25% receiving lorazepam. No significant difference in diarrhea, dystonia, or disinhibition was observed between the two arms. The authors conclude that the combination of lorazepam and metoclopramide was superior to metoclopramide alone in the prevention of cisplatin-induced nausea and vomiting, with sedation and amnesia more commonly observed in the combined regimen.

Adult↗
PubMed1989

Combined therapy for resectable head and neck cancer. A phase 3 intergroup study.

This Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeastern Cancer Study Group) phase 3 randomized prospective trial was opened for registration January 1985. It is an evaluation of the role of chemotherapy for previously untreated advanced stage resectable squamous cell carcinoma of the head and neck. As of March 1, 1988, there has been a total of 535 patients registered. There are 266 patients analyzable with 133 in each treatment group. The surgical, chemotherapy, and radiation therapy toxic reactions are in the tolerable range with the worst toxic reactions reported in those patients receiving both surgery and radiation therapy. Compliance continues to be a major challenge to patient accrual. The most common cause for cases not being randomized involves positive margins of surgical resection. Patient refusal or surgical complications are other common reasons.

Antineoplastic Agents↗
PubMed1988

Intracranial astrocytoma with diffuse bone marrow metastasis: a case report and review of the literature.

A 41 year old male presented with headache, lethargy, and ataxia and found to have a left temporal lobe mass and a leukoerythroblastic peripheral blood smear. The latter prompted an iliac crest bone marrow biopsy on which a diagnosis of metastatic glioma was made and verified by immunohistologic characterization. The patient was treated with cranial irradiation and simultaneous systemic BCNU (bis-dichloroethylnitrosurea) with complete response. This case with diffuse bone marrow involvement demonstrates that a glioblastoma is capable of extracranial metastases without previous intervention. From a review of reported cases of gliomas of extraneural metastasis, it is concluded that untreated gliomas are capable of vascular spread although less frequently than previously manipulated tumors.

Adult↗
PubMed1988

Treatment of advanced squamous cell carcinoma of the head and neck with isotretinoin: a phase II randomized trial.

Retinoids, the analogs of vitamin A, are active in vitro and in vivo against squamous cell carcinoma in animals and against certain epithelial precancers and cancers in humans. These data led us to design a prospective, multi-institutional, randomized phase II trial of isotretinoin in advanced head and neck squamous cell carcinoma. We randomly assigned 40 patients to receive isotretinoin or methotrexate, the best-studied and most active single agent for this disease. Overall, the study patients had extremely poor prognoses, i.e., low performance statuses and recurring disease after surgery and/or irradiation. Three objective responses (16%), including one complete response, occurred in the 19 evaluable isotretinoin-treated patients. Only one minor response (5%) occurred in the methotrexate-treated group. Toxicity occurred with both drugs, but was manageable and never life threatening in the retinoid group. These results and the established activity of retinoids in oral leukoplakia (a precursor of head and neck cancer) indicate the need for further study of this class of drugs in head and neck cancer.

Adult↗
PubMed1988

Excellent response to cis-platinum-based chemotherapy in patients with recurrent or previously untreated advanced nasopharyngeal carcinoma.

Twenty-four patients with recurrent and/or locally advanced nasopharyngeal carcinoma who received cis-platinum-based chemotherapy are reported. Twelve patients with recurrent disease previously treated with radiotherapy received cis-platinum-based chemotherapy. An overall response rate of 67% (8/12) and a complete response (CR) of 25% (3/12) were achieved. All the CR patients were treated with cis-platinum and 5-fluorouracil (5-FU) infusion. Twelve patients with locally advanced (stage IV) previously untreated nasopharyngeal carcinoma received cis-platinum-based chemotherapy. Eight of those patients received cis-platinum and 5-FU combination chemotherapy followed by radiation therapy. An overall response of 75% (6/8) and a complete response of 50% (4/8) were achieved by induction chemotherapy. Subsequent radiation therapy to the 6 responding patients (CR 4, PR 2) to chemotherapy increased the complete response to 100% (6/6). The other two stable patients refused further therapy and died in less than 1 year from locoregional disease. Four patients were treated with concurrent cis-platinum and radiation therapy. A complete response of 100% (4/4) was achieved.

Adolescent↗
PubMed1988

Response rate and toxicity with aziridinylbenzoquinone in patients with recurrent gliomas. A progress report.

Aziridinylbenzoquinone (AZQ), a quinone-containing lipophilic alkylating agent with molecular properties allowing for good penetration through the blood-brain barrier into the central nervous system, was evaluated in a phase II trial for recurrent gliomas patients. Twenty-four patients with computed tomography (CT) scan measurable disease were entered into the trial and received AZQ in doses of a weekly infusion of 15 mg/m2 (group A) and 17.5 mg/m2 (group B). Twenty-two patients were evaluable for both response and toxicity. There were no complete responses in this study. Partial response rates of 23% (3/13) and 11% (1/9) were achieved in group A and group B patients, for a median duration of response of 35 (range 10-106 weeks) and 19 weeks, respectively. The disease was stabilized in five patients from group A and in four patients from group B. Toxicity was mainly hematologic.

Adolescent↗
PubMed1988

An intensive, five course, alternating combination chemotherapy induction regimen used in patients with advanced, unresectable head and neck cancer.

Progress in the treatment of advanced squamous cell cancer (SCC) of the head and neck (H & N) has included the development of combination chemotherapeutic regimens that achieve impressive complete response (CR) rates using two to three courses therapy with minimal toxicity and good patient tolerance. Further improvements in these results will require intensification of induction regimens. Therefore, a five course, alternating combination chemotherapy induction trial was initiated in an attempt to test the feasibility and toxicity of a prolonged, intensive induction regimen in patients with advanced SCC of H & N. Courses 1, 3, and 5 consisted of fluorouracil as a 120-hour infusion (5FU-I) with cisplatin (CACP) as an intravenous (IV) bolus. Courses 2 and 4 consisted of 3 weekly doses of high-dose methotrexate (HDMTX) followed by 5FU (5FU-b) and leucovorin rescue (LR). Forty-six stage IV patients with SCC of H & N (85% T4 and 58% N3) were entered. Thirty-one patients completed the study and 15 did not. Twenty-one of the 46 patients (46%) achieved a CR. Twenty-five of the 46 patients had N3 neck disease, ten of these 25 achieved a CR (40%), and eight did not complete therapy. Of the 15 patients not completing this study, one patient achieved a CR and eight achieved a partial response (PR). Eight of 46 (17%) were removed from study for reasons of toxicity (6% to 13%) or tumor progression (2% to 4%). The remaining seven were removed due to intercurrent medical conditions (four uncomplicated pneumonias and one gun shot wound) or lost to follow-up (2). Myelosuppression, mucositis, and skin toxicity increased in frequency by the end of the trial but were acceptable and reversible. The activity of this five-course regimen is promising given the advanced disease status of patients treated. Consideration of concurrent medical conditions, patient compliance, intensity of medical, nutritional and social support, and levels of acceptable toxicity will be necessary in the design of future, intensive induction trials.

Adult↗
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↗