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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
PubMed1991

The Wayne State University experience with adjuvant chemotherapy of head and neck cancer.

Because of the poor results of standard therapy in patients with locally advanced head and neck cancers, chemotherapy is increasingly used to improve the outcome of these patients. In resectable disease, chemotherapy is being investigated before definitive treatments, after surgery, concurrent with postoperative radiotherapy, after radiotherapy, and for possible laryngeal salvage. In unresectable cancers, chemotherapy before, concurrent with, and following radiotherapy is being investigated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma: a radiation therapy oncology group study.

The results of radiotherapy alone for patients with locally advanced (stage III or IV) nasopharyngeal cancer (NPC) are poor in spite of the initial complete clearance. Twenty-seven patients (26 stage IV) were treated with concurrent standard radiotherapy and cisplatin 100 mg/m2 intravenously on day 1 and every 3 weeks for three courses. In 24 (89%) patients, complete response (CR) was achieved. The CR rate was higher for poorly undifferentiated cancer (100%). The major side effects were leukopenia (97%), anemia (54%), nausea and vomiting (81%), stomatitis (92%), and renal impairment (52%). Most of these side effects were either mild or moderate and reversible. All patients finished the radiotherapy dose (greater than 6,450 cGy), 19 (70%) had three courses of cisplatin, and eight had only two courses, six due to drug toxicity. Twenty-six patients with stage IV disease were compared with 78 patients treated with radiotherapy alone by the Radiation Therapy Oncology Group (RTOG). The disease-free survival (DFS), overall survival, and the incidence of distant organ metastasis appear to be better in the combined group. It was concluded that the combination of chemo-radiotherapy in patients with locally advanced NPC needs to be evaluated in a phase III randomized trial.

Adult↗
PubMed1990

The effects of chemotherapy on murine wound healing and orocutaneous fistula closure.

The effects of cisplatin and 5-fluorouracil on wound breaking strength and the rate of closure of an orocutaneous fistula were studied in 80 male rodents. Treatment rats received a total of 4.6 mg/kg cisplatin and 62 mg/kg 5-fluorouracil in six doses/12 days; control rats received 0.9 per cent saline. After treatment, 30 treatment and 30 control rats received a dorsal skin incision which was closed primarily. Wound breaking strength were tested at one, three and five weeks in ten rats from each group. An 8-mm orocutaneous fistula was made in the remaining ten treatment and ten control rats; the rate of closure was noted weekly. Cisplatin and 5-fluorouracil did not significantly impair wound breaking strength at one, three, or five weeks. The rate of closure of the orocutaneous fistula was not effected by cisplatin/5-fluorouracil. The chemotherapy caused severe facial cellulitis and death in four orocutaneous fistula rats. Combined chemotherapy with cisplatin and 5-fluorouracil should not interfere with planned surgical care of head and neck tumors. Concomitant antibiotic coverage, however, is advocated.

Animals↗
PubMed1989

Osseous regeneration after therapy in patients with head and neck tumors.

Four patients with head and neck tumors were observed by serial computed tomography (CT) during treatment. Osseous regeneration was demonstrated at sites of initial osteolytic destruction in two patients who responded to therapy. This regeneration was observed at 4 and 7 months, respectively, after the start of therapy. No such regeneration could be seen in the other two patients who did not respond to treatment. CT may be useful not only in demonstrating initial osseous invasion, but also in monitoring treatment response.

Adult↗
PubMed1989

Metastatic squamous cell carcinoma of an unknown primary localized to the neck. Advantages of an aggressive treatment.

Treatment of patients with squamous cell carcinoma (SCC) of an unknown primary localized to the neck is still controversial, particularly regarding advanced disease. We reviewed 41 such patients treated with surgery and/or radiotherapy (RT) (n = 25) or with combined modality treatment including chemotherapy (CH) (n = 16). The male to female ratio was 28 to 13, and the median age was 58 years (range, 32 to 94 years). There were 27 (66%) patients with poorly differentiated SCC and 8 with moderately differentiated or well-differentiated cancer. Twenty-three (56%) patients had N3 disease, 16 (39%) had N2, and 2 had N1. The majority of N3 patients have been treated with CH and RT (n = 12) or with RT alone (n = 9). The combined CH-RT was well tolerated, with no life-threatening toxicity. The complete response (CR) to CH-RT was 81% (11 patients have no evidence of disease [NED] currently). The median survival time of this group was 37+ months. Of the 25 patients who had surgery and/or RT as their first planned treatment, 7 (28%) have NED currently. The median survival time of this group was 24 months. Patients with N3 disease who received CH had a higher CR rate and a longer survival time as compared with those treated with surgery and/or RT, despite a higher (N3) stage of disease. These findings warrant further investigation in randomized cooperative studies.

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

Clinical trials with fluorinated pyrimidines in patients with head and neck cancer.

While it is estimated to be one of the most prevalent cancers in the world, cancer of the head and neck is an uncommon malignant tumor in the United States and accounts for only 5% of all malignancies. Head and neck cancer is a term that encompasses heterogeneous groups of patients. The most common histologic type is the squamous cell carcinoma. Cancer of the oral cavity is the most common site among the head and neck tumors. The majority of patients (70-80%) present with locally advanced (Stage III and IV) cancer. The standard treatments of surgery and/or radiotherapy have a high cure rate for patients with early disease (Stages I or II), but not for patients with locally advanced tumors. Local recurrence and persistent disease occur in more than 60% of patients present with advanced cancer, and approximately 10%-20% of all patients develop distant metastases. Chemotherapy is usually used for palliation in patients with recurrent and metastatic head and neck cancer at which time these patients have failed the definitive therapy of surgery and/or radiotherapy and the chances for salvage is almost nil. With the identification of more active cytotoxic agent(s) and combinations, chemotherapy is being investigated as part of multi-modality treatment in patients with previously untreated and locally advanced head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed1989

Chemotherapy following surgery for head and neck cancer. A Radiation Therapy Oncology Group Study.

The feasibility of chemotherapy of three courses of cis-platin and 120-h 5-fluorouracil (5-FU) infusion after definitive surgery, followed by standard radiotherapy, in patients with resectable locally advanced head and neck cancer was carried out in Radiation Therapy Oncology Group (RTOG). Seventy-nine percent of the patients had stage IV cancer, 65% of the tumors were moderately differentiated, and primary sites were 38% oropharynx and 28% larynx. Toxicity to chemotherapy was acceptable, with no life-threatening side effects. Nausea and vomiting were the most common side effects (78%) and were severe in 26%; 30% of patients experienced had leukopenia, 22% had anemia, 13% had thrombocytopenia, and 9% had renal impairment--all of which were mild and reversible. In six patients, chemotherapy was not given for medical conditions or because of patient refusal. Of 23 patients started on cis-platin and 5-FU postsurgery, 18 (78%) completed all three courses. Ninety-six percent of the patients finished adequate radiotherapy according to the protocol. With minimum follow-up of 24 months, 62% of the patients were alive. Of the expired patients, 5 died from other causes, without evidence of recurrence at the time of their death. It is our conclusion that chemotherapy with cis-platin and 5-FU infusion following definitive surgery is feasible on the group level, and a Phase III trial comparing this combined modality therapy to standard treatment of surgery and post-operative radiotherapy is underway by the Head and Neck Cancer Intergroup.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study.

Although there have been anecdotal reports of cardiac toxicity associated with fluorouracil (5-FU) therapy, this phenomenon has not been studied in a systematic fashion. We prospectively performed continuous ambulatory ECG monitoring on 25 patients undergoing 5-FU infusion for treatment of solid tumors in order to assess the incidence of ischemic ST changes. Patients were monitored for 23 +/- 4 hours before 5-FU infusion, and 98 +/- 9 hours during 5-FU infusion. Anginal episodes were rare: only one patient had angina (during 5-FU infusion). However, asymptomatic ST changes (greater than or equal to 1 mm ST deviation) were common: six of 25 patients (24%) had ST changes before 5-FU infusion v 17 (68%) during 5-FU infusion (P less than .002). The incidence of ischemic episodes per patient per hour was 0.05 +/- 0.02 prior to 5-FU infusion v 0.13 +/- 0.03 during 5-FU infusion (P less than .001); the duration of ECG changes was 0.6 +/- 0.3 minutes per patient per hour before 5-FU v 1.9 +/- 0.5 minutes per patient per hour during 5-FU (P less than .01). ECG changes were more common among patients with known coronary artery disease. There were two cases of sudden death, both of which occurred at the end of the chemotherapy course. We conclude that 5-FU infusion is associated with a significant increase in silent ST segment deviation suggestive of ischemia, particularly among patients with coronary artery disease. The mechanism and clinical significance of these ECG changes remain to be determined.

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

Chemotherapy of the squamous cell lung cancer LC-12 with 5-fluorouracil, cisplatin, carboplatin or iproplatin combinations.

The combination of Cis-dichlorodiammineplatinum (II) (CisDDPt) + 5-Fluorouracil (5-FU) was compared with two CisDDPt analogues + 5-FU [Iproplatin (CHIP) + 5-FU and Carboplatin (CBDCA) + 5-FU] for relative efficacy against advanced stage squamous cell lung tumors (LC-12) in Balb/c mice. At equitoxic dosages, the numbers of regressions and cures were similar for the three combinations (5-FU/CISDDPt 2/10 PR's, 2/10 CR's, 2/10 cures; 5-FU/CBDCA 1/10 PR's, 5/10 CR's, 3/10 cures; 5-FU/CHIP 1/10 PR's, 3/10 CR's, 3/10 cures). The tumor growth delay among the mice not cured was slightly superior in the 5-FU/CisDDPt regimen. All the agents were active singly against this tumor model. Based on these results, the substitution of CBDCA or CHIP for CisDDPt in a FU regimen did not offer a cytotoxic advantage. Because of different dose limiting toxicities for the platinum compounds the possibility exists that these analogues could be used in drug combinations in substitution for CisDDPt.

Animals↗
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↗
PubMed1988

Anal carcinomas: new combined modality treatment approaches.

In the past, anal cancers were treated by abdominal-perineal resection with permanent colostomy. Radiotherapy was used only for inoperable patients or those with unresectable cancers. With improvements in the delivery of radiation, external radiotherapy, brachytherapy, or combinations of the two were used in patients with localized disease of less than 4 cm in size with results similar to surgical resection. Unfortunately, up to 25% of these patients developed severe necrosis necessitating permanent colostomy. During the past decade a considerable change in the treatment of these cancers occurred. Chemo-radiotherapy has made surgical resection unnecessary in the majority of patients. The primary treatment is now the combination of mitomycin-C and 5-fluorouracil (96-hour infusion), plus radiation (3,000 cGy).

Anus Neoplasms↗