Hussein Khaled

Thymidine kinase (TK) and tissue polypeptide specific antigen (TPS) were determined in breast cancer (BC) patients (n = 83), normal healthy women (n = 30) and 18 women with different benign mastopathies. Mean serum levels of TK and TPS in BC patients showed significant increases from their corresponding levels in healthy women and those with benign breast diseases. Diagnostic sensitivity of TK and TPS was 47% and 58% respectively at the selected cut-off values 8 U/L for TK and 110 U/L for TPS (96% specificity). Pre-operative serum levels of TK and TPS showed significant correlation with the stage of disease and with other classical prognostic factors; clinical stage, tumour size, lymph node involvement and distant metastasis. Nineteen BC patients were followed-up by serial monthly measurements of TK and TPS (4-10 samples). Both markers seemed to be valuable in monitoring drug efficacy. TK and TPS were able to detect systemic recurrence before clinical diagnosis (average 2 months lead time). TPS was greatly affected by liver diseases.

Response to endocrine therapy and its relationship to the clinical features of the disease were studied in 84 Egyptian patients with inoperable locally advanced or metastatic breast cancer. Twenty-four premenopausal patients were treated by oophorectomy with or without concurrent prednisolone. Only one of 20 evaluable patients achieved an objective response. Median time to progression for premenopausal patients was 3 months. Sixty postmenopausal patients received tamoxifen 10 mg twice daily either alone or with prednisolone. Fourteen of 57 (25%) evaluable patients achieved an objective response (four complete remission, 10 partial remission). Median duration of response was 13 months and median time to progression for all postmenopausal patients was 5 months (range 1-30 months). The outcome for postmenopausal patients was similar to that found in a parallel study at Guy's Hospital, London. The response rate for premenopausal Egyptian patients was, however, disappointing and lends support to the claim that breast cancer in Egyptian women is particularly aggressive.

We evaluated the efficacy of epirubicin in a phase II trial in breast cancer, as well as its cardiac toxicity. The study was carried out on 40 female patients with advanced, metastatic, or recurrent breast cancer. The patients were grouped into two groups: group I received 30 mg/m2 epirubicin weekly, and group II 90 mg/m2 epirubicin every 3 weeks. Cardiac monitoring was by ECG, roentgenography, echocardiography and endomyocardial biopsies. Clinical results were 35.3% overall response in group I, and 50% overall response in group II. No untoward cardiac toxicities were encountered. We conclude that epirubicin is an effective agent in breast cancer with relatively little cardiac toxicity.

Seventy-one patients with T2 and T3 bladder cancer were randomized to receive either two courses of epirubicin 120 mg/m2 i.v. push every 21 days pro-operatively, and four additional courses post-operatively (group I = 34 patients), or radical surgery (group 11 = 37 patients). At a median follow-up of 24 months (range 22 months to 38 months) 25 patients from group I and 14 patients from group II are still alive and disease-free. The estimated two-year disease-tree survival percentages were 73.5 and 37.9%, respectively (P = 0.05). After initial chemotherapy, resected specimens were subjected to histopathologieal study of chemotherapeutic effects. Necrosis was detected in 95% of cases with squamous cell carcinoma and in 57.3% of cases with transitional cell carcinoma. We conclude that the benefit which was obtained by pre-operative and post-operative chemotherapy with epirubicin is promising and may represent a significant improvement in the treatment of patients with carcinoma of the bilharzial bladder.

Using two different agar based double-layer culture assays, 16 bilharzial urinary bladder carcinoma samples were evaluated for the in-vitro effects of 1 hour's exposure to alpha 2 interferon at 3-log concentrations. Ten of these tumor samples were evaluable for drug sensitivity testing. In the liquid top layer dye exclusion assay, 40%, 60%, and 60% of the 10 tested tumor samples were sensitive to alpha 2 interferon 100, 1,000, and 10,000 units/ml respectively, and 25%, 25%, and 63% of 8 tumor cell suspensions were sensitive to the above drug concentrations when the human tumor colony forming assay was performed. Comparing both assays in 24 different drug measurements, there was a 71% concordance rate. All of the 7 discordant measurements were sensitive in the dye exclusion and resistant in the clonogenic assays. Thus, bilharzial bladder cancer cells are relatively sensitive to the in-vitro effect of alpha 2 interferon, especially of higher concentrations, and a phase II clinical trial deserves consideration.

Ifosfamide has definite efficacy in many malignant tumours, including breast cancer. In the present study we substituted cyclophosphamide with ifosfamide in the combination CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) regimen in 25 patients with breast cancer whose disease was refractory to CMF or who had relapsed after previous response. Ifosfamide was given in an i.v. infusion at a dose of 1.2 g/m2 daily for 5 days, together with mesna as a uroprotector (at 20% of the ifosfamide dose). Methotrexate was given at a dose of 40 mg/m2 and 5-fluorouracil was given at 600 mg/m2, both by i.v. push. Courses were repeated every 21 days. The 24 evaluable patients received 3-12 courses (average, 5 courses); results included a complete remission in 3 patients (12.5%) and a partial remission in 3 (12.5%). Among the remaining patients, improvement was seen in 4 (16.6%); stable disease, in 7; and progressive disease, in 7 (29.2%). The complete responses lasted for 11+, 13+, and 15+ months, and partial remissions, for 2, 6, and 9 months. The responses were detected in soft-tissue as well as visceral lesions, but not in bony lesions. The responders remain under follow-up. This study shows the efficacy of ifosfamide-containing chemotherapy in breast cancer. As toxicities were tolerable, higher doses of ifosfamide could safely be used in these patients. Use of this combination as first-line therapy in breast cancer could be considered for a future study. © 1990 Springer-Verlag.

Since 1976, a series of phase II studies with screening of various chemotherapeutic agents in invasive bladder cancer have been conducted at the National Cancer Institute, Cairo. Different drugs were screened, one by one, in groups of 20-25 patients with inoperable, metastatic, or recurrent carcinomas. Evaluation was done by clinical bimanual examination, radiography, sonography, cystoscopy, and urine cytology. In these trials bleomycin and doxorubicin were ineffective. Tenoposide, 5-fluorouracil, methotrexate, and cisplatin had minimal or moderate effect (response rates 4-16% More pronounced effect was found for dibromodulcitol, cyclophosphamide, pentamethylmelamine, etoposide, hexamethylmelamine, ifosfamide, vindesine, vincristine, and epidoxorubicin (response rates 18-60% Some complete responders remained in response for a period of 3-7 years. Drugs seemed to be more effective in metastatic than in local lesions. ©1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Some 95 samples representing the phosphates of Jordan were taken from Esh-Shidiya, Hasa, Mujib, Qastal, Ariesh, Rusiefa and North Jordan phosphates. They were analysed for U, P and Ca. The U contents are found to increase towards Ruseifa in the N. The U3O8/P2O5 ratio is a better indicator for U distribution than the absolute values of U. This study indicates that each locality has its characteristic ratio, and the mean ratio for each locality increases towards N Jordan. Thus, while Esh-Shidiya has 2.8 ppm U for each 1% P2O5, Rusiefa has 5.39 ppm U for each 1% P2O5. It is ths recommended that if the fertilizer industry is going to utilize U from the Jordan phosphate they should use the N Jordan deposits (ie Qastal, Rusiefa, Samu) and not Esh-Shidiya phosphate.-Authors

The results of hexamethylmelamine therapy in 20 patients with advanced squamous cell head and neck cancer are reported. No patient had previously received chemotherapy. The dose of hexamethylmelamine was 8 mg/kg/day p.o. There was partial response in 3/20 (15%) patients. The duration of the response was 6-10 weeks. Twelve of 20 (12/20) patients had stable disease for a median of 8 weeks (range: 4-18 weeks). Hexamethylmelamine was well tolerated with the only significant toxicity being mild nausea and vomiting. This drug deserves further evaluation in the treatment of head and neck cancer.