Cases Of WHO Grade Research Articles

Oral estramustine and cyclophosphamide in patients with metastatic hormone refractory prostate carcinoma

Nearly all cases of metastatic prostate carcinoma progress, after hormonal ablation, to a hormone refractory status. To the authors' knowledge no standard chemotherapy for patients with hormone refractory prostate carcinoma (HRPC) exists. In a prospective study, the efficacy and toxicity of an oral combination of estramustine and cyclophosphamide were evaluated. Between March 1996 and April 1998, 32 consecutive patients (median age 74 years; range, 53-84 years) with metastatic HRPC were treated with oral estramustine (10 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 14 days every 28 days. Inclusion criteria were previous complete androgen blockade, antiandrogen withdrawal evaluation, and clinical or biochemical disease progression. Response assessment was based on a decrease > or =50% in the prostate specific antigen (PSA) level associated with improvement (or no worsening) in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and relief of bone pain (if present). All patients were evaluable for efficacy and toxicity. PSA levels decreased by at least 50% in 14 patients (43.7%) (95% confidence interval, 26.5-60.9), remained stable in 12 patients (37.5%), and rose in 6 patients (18.8%). ECOG PS was 0 in 5 of 14 patients, improved from 1 to 0 in 7 patients, and remained unchanged in 2 patients. Bone pain, present in 8 of 14 patients, disappeared in 7 and was partially relieved in 1. The median duration of response was 30 weeks (range, 8-88+ weeks). An objective partial response was obtained in two cases. Toxicity was mild and mainly gastrointestinal (World Health Organization [WHO] Grade 1). No cases of WHO Grade 3-4 hematologic toxicity occurred. The oral combination of estramustine and cyclophosphamide appears to be safe and effective in patients with HRPC. In responding patients its use shows a clinical benefit in terms of improvement of ECOG PS and pain control.

ASSOCIATION OF HEMORHEOLOGICAL PARAMETERS AND RISK OF STROKE IN HYPERTENSIVES OF INDIAN ORIGIN

The blood viscosity parameters of one hundred and fifty cases of WHO grade I and II hypertension of Indian origin, on treatment with calcium antagonists, were measured and a six-monthly follow up was conducted for a period of three years. The whole blood viscosity (WBV), plasma viscosity (PV), red cell rigidity (RG) and hematocrit (Hct) were monitored. Occurrence of stroke was considered as the outcome variable and it was observed that sixteen cases of stroke occurred during the follow up period (10.7% incidence). After excluding known risk factors of age, sex, addictions, blood pressure levels, cholesterol levels and underlying diseases, it was observed that an increased whole blood viscosity > 6 centiPoise was associated with an increased risk of stroke (Relative risk 2.9, 95% confidence interval 2.2 to 3.7). An increased red cell rigidity in a hypertensive patient was found to be an independent risk factor for stroke. Patients with red cell rigidity greater than 4 had 4 times (Relative risk 3.6, 95% confidence interval 3.2 to 4) higher risk of stroke as compared with patients with red cell rigidity levels less than 4. Treatment with drugs modifying the rheological profile and aiming at improving the red cell deformability should thus be considered in hypertensive patients in an attempt to prevent the occurrence of stroke.

Is Continuous 24-Hour Infusion of 5-Fluorouracil plus High-Dose Folinic Acid Effective in Patients with Progressive or Recurrent Colorectal Cancer?

Background: To evaluate the therapeutic activity of 24-hour continuously infused 5-fluorouracil (5-FU) modulated by high-dose folinic acid in patients with metastatic colorectal cancer who had recurred or progressed following mainly bolus 5-FU/folinic acid chemotherapy. Patients and Methods: Forty-two patients with a median age of 59 years (45–76) were enrolled. Karnosfky status was 90% (80–100), previous chemotherapy regimen bolus 5-FU/folinic acid (n = 33, 79%) or 24-hour continuous 5-FU ± interferon α₂ (n = 9, 21%). Chemotherapy was given as a weekly infusion of 500 mg/m² folinic acid over 2 h followed by a 24-hour continuous infusion of 2,600 mg/m² 5-FU for 6 consecutive weeks followed by a 2-week rest period. Results: No complete but 6 partial responses were observed (ORR: 14%, CI_95%: 3.5–25.1%) with a median response duration of 7.3 months (range: 1.4–10.6). The median survival from the start of continuous infusion of 5-FU was 11.6 months (range: 2–27, CI_95%: 9.4–13.8) and the 1-year survival rate was 46%. Disease stabilization and minor responses were achieved in another 25 patients (61%). WHO grade III/IV diarrhea occurred in 26% of patients, mucositis, nausea/vomiting and hand-foot syndrome in 5% each. Two cases of WHO grade III anemia and leukocytopenia were observed (5% each). Dose reductions had to be performed in 11 patients because of unacceptable diarrhea with subsequent stop of treatment in 2 patients. Progressive disease while receiving previous bolus 5-FU chemotherapy was associated with a lower response rate, shorter progression-free interval and overall survival compared to response and survival of patients who had achieved temporary disease stabilization during previous bolus 5-FU therapy. Conclusions: Continuous infusion of 5-FU/folinic acid displays activity in pretreated and refractory colorectal cancer with acceptable toxicity. Patients who had achieved disease stabilization or objective remission with previous 5-FU bolus therapy appear to be more likely to benefit from second-line treatment. Questions remaining to be addressed include the optimal starting dose of continuously infused 5-FU and whether the dose of folinic acid can be reduced or completely eliminated with respect to toxicity and health economics.

ARTERIAL CHEMOEMBOLIZATION WITH EPIRUBICIN IN UNRESECTABLE HEPATOCELLULAR-CARCINOMA IN CIRRHOSIS

No reliable therapy has yet been established for unresectable hepatocellular carcinoma (HCC). Encouraging data in terms of response rate and survival have been reported with intra-arterial chemotherapy combined with venooclusive materials, specifically ethiodized oil and gelatin sponge. To evaluate the activity and tolerance of a new chemoembolization protocol in cirrhotic patients with HCC, 22 patients were treated with epirubicin (50 mg) and ethiodized oil (10-15 ml), administered through hepatic arterial catheters, followed by gelatin sponge. Patient characteristics were: median age 70 years (range, 59-77); ECOG performance status 0-1 in 15 and 2 in 7 cases; Child's A disease in 11 and B in 11; TNM stage II in 9, stage III in 3 and stage IVA in 10 cases. Histologically documented cirrhosis was present in all cases. A total of 53 courses of therapy has been delivered. All patients were evaluable for response and toxicity. Three partial remissions (13%), 2 stabilizations of disease and 17 progressions have been observed. Median time to progression was 4 months, with a median survival of 7.6 months (range, 1-26+ months). Significant differences in survival (p = 0.001) have been observed between patients at stage II-III (21 months) and those at stage IVA (3 months), and between patients with Child's A disease (10 months) and Child's B disease (4 months) (p= 0.02). The treatment was well tolerated, with only 2 cases of WHO grade I pain and 2 cases of grade I fever. In conclusion, our results indicate that the schedule has only limited activity and does; not seem to offer any sure advantage over other treatments modalites in HCC.