A simple strategy for breakpoint fragment determination in chronic myeloid leukemia.

Molecular characterization is considered a part of the routine work-up of chronic myeloid leukemia (CML) cases. Southern blot analysis using the universal BCR (UBCR) probe on BglII-digested DNA samples is the most commonly used technique, while employing the human 3' bcr probe (PR-1) is usually considered a complementary tool. In this study, we tried to develop a simple and economic strategy for molecular characterization of CML using the 3' probe as it has been shown to be the one capable of locating the breakpoint site. Seventy-eight cases of CML were studied. Molecular analysis was performed using the Southern blot technique. DNA was digested with Bam HI, BglII, EcoRI, and XbaI. Hybridization was performed using the human 3' bcr (PR-1) probe. BamHI and BglII could differentiate fragment 1 (F1) showing rearrangement (R) with Bam HI and germline configuration (G) with BglII; F2/3 showing R with both, and F4 showing R with BamHI and G with BglII. F2/3 cases were further divided by HindIII enzyme into F2 showing (G) and F3 showing (R). Fragment 0 showed G with both, but R with EcoRI and/or XbaI, while 3' deletion gave G with all four enzymes. Our results showed a relative incidence of 6.4% for F0, 20.5% for F1, 32.1% for F2, 19.2% for F3, 15.4% for F4, and 6.4% for 3' deletion. Sixty cases were evaluated clinically and hematologically and were followed up for disease evolution and survival. They included 32 cases in early chronic phase, 24 in late chronic phase, two in acceleration, and two in blastic crisis. No significant correlation was encountered between the breakpoint site and any of the clinical and hematological data except those patients with 3' deletion who showed a very short survival. The study emphasizes Southern blotting as the method of choice for molecular characterization of CML and offers a simple and economic strategy for diagnosis and determination of breakpoint fragment.

A phase II study of gemcitabine plus cisplatin chemotherapy in advanced bilharzial bladder carcinoma.

Bilharzial bladder cancer represents a distinct clinicopathological entity. To investigate whether gemcitabine-cisplatin is also active against bladder cancer of bilharzial origin, we performed a phase II study of previously untreated patients with stage III/IV disease. Standard eligibility criteria were used. Patients received gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 and cisplatin (70 mg/m(2)) on day 2 of every 28-day cycle. The 32 males and 5 females had a median age of 59 years (range: 29-81 years). Of 33 evaluable patients, 8 (24%) achieved complete responses, and 10 (30%) partial responses, for an overall response rate of 55%. 3 patients had minor responses. Responses were observed at all disease sites including lung and liver lesions. Myelosuppression was significant but manageable. Non-haematological toxicity was limited mainly to nausea and vomiting and raised liver enzymes. Thus, these data suggest that gemcitabine plus cisplatin induces high response rates in patients with bilharzial bladder cancer with a moderate toxicity profile.

Allelic instability as a predictor of survival in Egyptian breast cancer patients.

This work was designed with the purpose of determining whether the presence of allelic imbalances (AI) such as microsatellite instability (MSI) and loss of heterozygosity (LOH) in chromosomes 2, 11, 13, and 17 in primary breast cancer could be used as prognostic indicators of patient survival. The DNA from breast cancers removed from 29 patients who were followed-up for up to five years was analyzed for MSI and LOH using a panel of 24 markers located at chromosome 2 (TPO, D2S131, D2S144, D2S171, D2S177, D2S119, D2S123, D2S147 and D2S136), chromosome 11 (C-RAS, Int-2, D11S940, D11S912), chromosome 13 (D13S289, D13S260, D13S267, D13S218, D13S263, D13S155, and D13S162), and chromosome 17 (D17S513, TP53, D17S855, and D17S785). The frequency of AI in the markers studied ranged from 30-55%, being highest for D11S912, D2S171, TP53 and D17S855. Univariate analysis showed association between overall survival rate and AI in 9 out of the 24 markers tested. Five of them were located at the area of the mismatch repair gene (MMR)-2 gene, two at 11p, one at 13q and one at 17p. Using multivariate analysis, it was observed that only pathological and clinical stage (defined as stage II or not) and AI at D2S171, D11S912, or D17STP53 generated significant predictive models for survival.

Colorectal cancer in Egyptian patients under 40 years of age.

Although colorectal cancer is not a common cancer in Egypt, the age distribution of the disease shows that a high proportion occurs in children and adults under 40 years of age. We reviewed the records of 1,608 colorectal cancer patients treated in 4 cancer hospitals in Egypt during a period of 3 to 10 years. The hospitals in which about 85% of all colorectal cancer cases in Egypt were seen included Egypt's 2 major cancer centers, The National Cancer Institute (NCI) in Cairo and Tanta Cancer Center (TCC) in the mid-Nile Delta region, and 2 major university hospitals, Assiut University in South Egypt and Ain Shams University in Cairo. Our review showed that patients younger than 40 years represented 35.6% of all patients in the 4 cancer hospitals, and that these rates were similar among the hospitals and for the years reviewed. The male-to-female ratio increased from 1.0 to 1.7 for the age groups ranging from 0-9 and 30-39 years, and increased from 1.0 to 1.5 for the age groups ranging from 40-49 to over 60 years. More than half of all the patients had rectal tumors, and about 90% of the cancers were adenocarcinomas; 30.6% of patients younger than 40 years, compared with 13.8% of older patients, had mucin-producing tumors. This study confirmed the occurrence of a high colorectal cancer rate in young Egyptians, and it opens the door to future epidemiologic studies to identify causes and risk factors of this disease pattern in Egypt.

Combination chemotherapy for advanced bilharzial bladder carcinoma.

BACKGROUND: Carcinoma of the bilharzial bladder, the most common cancer in Egyptian patients has been, until recently, largely treated by surgery. We have studied the activity of a series of single agents in phase II trials and identified a number of active agents. Here we report the results of a trial in which therapeutic combinations of the most active agents were administered in alternating cycles to patients who had never received chemotherapy. PATIENTS AND METHODS: The study included 30 patients with histologically proven inoperable (20), recurrent (5, 2 of whom subsequently developed metastases), or metastatic disease (5). There were 27 males and 3 females, with a median age of 48.5 years (range 29-65 years). Fourteen patients had squamous cell carcinoma, 12 had transitional cell carcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiated carcinoma. Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1) and vincristine (1.4 mg/sqm i.v., days 1 and 8) alternating with etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1 to 5) and ifosfamide (1800 mg/sqm i.v. infusion over 2 hours, days 1 to 5). Mesna was given as a uroprotector at 40% of the ifosfamide dose at 0, 4, and 8 hours after the ifosfamide infusion. Courses were repeated every 3-4 weeks. RESULTS: Among the 22 evaluable patients, 8 (36.5%) had a partial and one (4.5%), a complete response, giving a response rate of 46%. Three more patients had responses that were less than a partial remission, and 6 patients showed disease stabilisation on chemotherapy. Toxicities were tolerable and consisted mainly of myelosuppression. Results were further analysed in relation to pathologic subtype, disease status at the start of chemotherapy, and the delivered dose intensity. No relationship was found between any of these parameters and response to therapy. CONCLUSION: Advanced bilharzial bladder cancer is relatively sensitive to combination chemotherapy, but complete remission and prolonged survival is rare in this subgroup of patients with advanced disease. Further studies will be needed to determine the relative efficacy of single agents and drug combinations.

A phase II study of epirubicin in breast cancer.

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.

Pediatric non-Hodgkin's lymphoma abdominal presentations: a comparative study between two treatment regimens at the National Cancer Institute Cairo.

Abdominal presentations of pediatric NHL are rarely amenable to complete surgical resection. Chemotherapy is the hallmark of treatment for pediatric NHL. Treatment of various types of this disease including intra-abdominal NHL in children with various protocols have not exceeded 54 per cent two-year disease-free survival. We have attempted to study and compare the effects of two treatment regimen upon two groups of previously untreated children up to the age of 16 years who presented to the Pediatric Oncology Unit at the NCI. The first group included 18 children who presented between 1983 and 1985 and were treated by a modified St Jude regimen: while the second group of patients was comprised of 19 children who presented between 1985 and 1987 and were treated by a multi-national protocol: the MCP 842. The two groups will be compared with respect to various patient characteristics, response to therapy and their two-year disease-free survival as well as overall survival.

Prolonged disease-free survival in pediatric non-Hodgkin's lymphoma using ifosfamide-containing combination chemotherapy.

Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16 per cent of pediatric malignancies reported to the National Cancer Institute (NCI) in Cairo. The adopted treatment for these cases was, from 1982 to July 1985, a modified St Jude's regimen consisting of: vincristine, cyclophosphamide, adriamycin, prednisone and intrathecal methotrexate for the first 6 weeks for induction, followed by cranial irradiation for cranial prophylaxis. Patients in remission received maintenance therapy for 18 months. Of 32 patients complete remission (CR) was achieved in 24 patients (75 per cent); partial remission (PR) in one patient (3 per cent); five patients showed no response (15 per cent) while two patients died during the induction phase. At 60+ months follow-up, 60 per cent of cases are still alive, disease-free, and overall survival is 66 per cent. A new protocol was adopted in 1985, consisting of alternating cycles: A and B, for 4-8 cycles. Cycle A: cyclophosphamide, high dose ara-C, adriamycin, and vincristine. Cycle B: ifosfamide, methotrexate, VP 16, with intrathecal methotrexate. The response in 39 cases is: CR in 31 cases (82 per cent); PR in four cases (10 per cent); no response in three cases (8 per cent). At 60+ months, the disease-free survival is 60 per cent, and overall survival 80 per cent. This new protocol has the advantage of: short duration of therapy and so better patient compliance, no maintenance therapy or cranial irradiation with its sequelae in the future. Moreover, it has a better overall survival.

A randomized pilot study of high-dose epirubicin as neoadjuvant chemotherapy in the treatment of cancer of the bilharzial bladder.

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 pre-operatively, and four additional courses post-operatively (group I = 34 patients), or radical surgery (group II = 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-free survival percentages were 73.5 and 37.9%, respectively (P = 0.05). After initial chemotherapy, resected specimens were subjected to histopathological 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.

Ifosfamide, methotrexate, and 5-fluorouracil: effective combination in resistant breast cancer.

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.

Chemotherapy in invasive carcinoma of the bladder. A review of phase II trials in Egypt.

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.

Hepatic angiosarcoma among Egyptian farmers exposed to pesticides.

A greatly increased incidence of hepatic angiosarcoma (H.A.S.) among Egyptian farmers involved in pest-control spraying operations attracted our attention. Fourteen patients were diagnosed at Ain Shams University Hospital between the years 1980-1984 as having H.A.S. Eleven were males and 3 females with an average age of 49 years, and a male:female ratio of 3.8:1. Eleven patients reside in Lower Egypt and 3 in Upper Egypt. Ten out of the 14 patients had a definite history of a direct chronic recurrent exposure to agricultural pesticides of variable chemical nature, throughout the year. The period of exposure ranged from 11-20 years with an average of 14 years. The other 4 patients had no history of exposure to any of the known carcinogenic factors. This significant increase in angiosarcoma among farmers involved in pesticide spraying suggests that agricultural pesticides might play a role in the genesis of H.A.S. in Egypt.

Pediatric Hodgkin's disease in Egypt.

A consecutive group of 242 children with Hodgkin's disease attending the National Cancer Institute, Cairo during the years 1975-1980 were studied. Males predominated representing 76.85% of cases. Age distribution was similar to other African countries with an earlier presentation than the US. The most common histopathologic types was the mixed cellularity 60.74% of patients. Late Stages III and IV represented 63.22%, with a high tumor burden. Celiotomy in 154 cases detected more tissue involvement than clinical assessment. Its results coincided with lymphography in 68% of the cases. It showed 7 cases with schistosomal hepatic fibrosis. As schistosomal infestation is still prevalent in rural areas of Egypt, celiotomy seems mandatory in the cases studied to accomplish proper staging.