Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas.

BACKGROUND: The aim of the study was to evaluate the safety and efficacy of the raltitrexed/5-fluorouracil/levofolinic acid combination regimen as first-line chemotherapy for elderly patients with advanced/metastatic colorectal cancer. PATIENTS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 2 mg/m(2) i.v. plus levofolinic acid and 5-fluorouracil according to the De Gramont' schedule given every 2 weeks as first-line chemotherapy. Patients were re-evaluated after six cycles and chemotherapy was continued up to tolerance or disease progression. RESULTS: Seventy patients aged >/=65 years were accrued from 11 centers between September 2001 and July 2002. According to the intention-to-treat analysis, the overall response rate was 35% (95% CI 29.5% to 40.5%) including one complete response (1%) and 24 partial responses (34%). Twenty patients (31%) showed a stabilization of disease for a tumor growth control rate of 64% (95% CI 57% to 71%). The median overall survival was 12.5 months and the median time to disease progression was 6.5 months. No toxic deaths or allergic reaction were recorded. Grade 4 toxicities were non-existent. The main hematological toxicity was grade 3 neutropenia, which occurred in 9% of patients, and grade 3 anemia in only one case, while no case of graded 3 thrombocytopenia was observed. Grade 3 non-hematological toxicities were asthenia (11%), transient increase of transaminases (10%) and diarrhea (4%). CONCLUSIONS: The results of this study suggest that the raltitrexed/5-fluorouracil/levolofinic acid combination is an effective and well tolerated regimen for the treatment of elderly patients with advanced colorectal cancer. Its ease of administration and patient's tolerance warrant further investigation over 5-fluorouracil/folinic acid regimens.

Cisplatin and vinorelbine in advanced and/or metastatic adenocarcinoma of the endometrium: a new highly active chemotherapeutic regimen.

PURPOSE: To date the systemic treatment of recurrent and/or metastatic adenocarcinoma of the endometrium (EAC), using both chemotherapy and hormonotherapy (HT), is far from satisfactory. The significant activity of vinorelbine (VNR), a relatively new semisynthetic vinca alkaloid, demonstrated in advanced breast cancer, bronchial adenocarcinoma, and in head and neck cancer, prompted us to carry out a phase II trial employing the combination of cisplatin and VNR in a pluri-institutional series of patients with recurrent and/or metastatic EAC. PATIENTS AND METHODS: Thirty-five patients affected by recurrent and/or metastatic EAC have been treated with CDDP 80 mg/m2 on day 1 plus VNR 25 mg/m2 i.v. bolus on days 1 + 8. This cycle was repeated every 21 days. After three cycles patients were restaged for objective response. Analysis of response rate and duration, overall survival, and toxicity pattern were the main aims of the study. RESULTS: Twenty out of thirty-five patients achieved a major objective response for an overall response rate of 57% (95% confidence limits (CL): 39%-74%). Four patients had a complete response (11%; 95% CL: 3%-27%) with a median progression-free survival (PFS) of eight hundred fourteen days, while sixteen patients had a partial response (46%; 95% CL: 29%-63%) with a median PFS of one hundred eighty-four days. Six patients had stable disease and nine progressed. All patients who achieved a clinical complete response had only a single site of disease at entry, but no association was noted between number of involved sites and likehood of achieving PR. Median overall survival was 240 days, while that of patients with complete and partial response was 855 and 300 days, respectively. Treatment was quite well tolerated with few cases of grade 3-4 myelosuppression. Alopecia was virtually absent and neurotoxicity was mild. One patient complained of an acute pain syndrome at the tumor site. CONCLUSIONS: The CDDP + VNR regimen is quite active against recurrent and/or metastatic endometrial adenocarcinoma, at least in terms of objective response rate which is among the highest ever reported in medical literature. However. duration of objective response and median overall survival are in the disappointing range reported for other regimens. In our opinion the CDDP plus VNR regimen is good enough to be compared to the anthracycline-based regimens and may represent the basis for future development of newer active polychemotherapeutic schedules.

Treatment of refractory metastatic breast cancer with 5-fluorouracil and levofolinic acid as 48 hours continuous venous infusion.

Twenty-four consecutive patients with metastatic breast carcinoma (MBC) refractory to first line chemotherapy were treated with high-dose folinic acid (FA) 100 mg/m2 diluted in 250 cc of normal saline as 2 hour infusion followed by 5-fluorouracil (5FU) 400 mg/m2 bolus then 5FU 600 mg/m2 as continuous infusion for 22 hours. This therapy was repeated for 2 consecutive days. Chemotherapy was repeated every 15 days. All enrolled patients were evaluable for objective response. A complete response was achieved in 1 patient (4%) and a partial response in 6 cases (25%) for an overall response rate of 29% (confidence limits 18%-39%). The median duration of objective responses was 8.4+ months (range 3.0+/12.8). Six patients showed no change (25%) with a median duration of 4.0 months 11 patients progressed (46%). A subjective improvement in tumor-related symptoms was reported by all responding patients and in 3 patients with no change. Most patients (7/10) with symptomatic bone lesions had a subjective improvement with reduction in analgesic drugs consumption. Objective responses were observed at all sites of disease. In fact, responses were seen in the skin liver lung bore and rodal metastases. The median overall survival was 13.0+ months (range 4.0/16.2+). Over a total of 160 cycles (a mean of 6.6 cycles/patient) grade 1-2 leukopenia was seen in 9 patients (37%) grade 1 thrombocytopenia in 4 patients (17%) and grade 1 anemia in only 2 cases (8%). Grade 3-4 leukopenia or thrombocytopenia were not seen. Phlebitis at the injection vein occurred in 3/10 patients (30%) which refused to implant a central line. In patients with a central line or a port-a-cath no cases of vascular, toxicity were seen. Gastrointestinal toxicity was very mild with 9 patients (37%) suffering from grade 1-2 nausea/vomiting 6 patients (25%) complaining of grade 1-2 diarrhea and 6 patients with grade 1-2 stomatitis. Hand-foot syndrome was observed in only 1 patient. No cases of grade 3-4 gastrointestinal toxicities have been, observed. No cases of cardiotoxicity and/or neurotoxicity were recorded. The combination of high-dose FA and 5FU given as 48 hour continuous venous infusion every 2 weeks is active, at least in terms of objective response rate and tumor-related symptoms palliation against anthracycline-refractory MBC. These results compare favorably with bolus administration of FA and 5FU or other salvage regimens.

Single agent 2',2'-difluorodeoxycytidine in the treatment of metastatic urothelial carcinoma: a phase II study.

PURPOSE: To evaluate the therapeutic activity and toxicity of gemcitabine in the treatment of metastatic urothelial carcinoma. PATIENTS AND METHODS: Twenty-four consecutive patients with recurrent- and/or metastatic urothelial carcinoma pretreated with first line cisplatin-based chemotherapy were treated with gemcitabine 1000 mg/m2/week intravenously diluted in 250 cc of normal saline as 20 minutes infusion for 3 consecutive weeks followed by a 1 week rest period. Chemotherapy was repeated every 28 days. RESULTS: All enrolled patients were evaluable for objective response accordingly to an intent-to-treat analysis. A complete response was achieved in 1 patient (4%) and a partial response in 6 cases (25%) for an overall response rate of 29% (confidence limits 18%-39%). The median duration of objective responses was 7.4+ months (range 3.0+/12.8). Six patients showed no changes (25%) with a median duration of 4.0 months. A subjective improvement in tumor-related symptoms was reported by all responding patients, and in 3 patients with no change. Six out of 9 patients with symptomatic bone lesions had a subjective improvement with reduction in analgesic drugs consumption. Objective responses were observed at all sites of disease. The median overall survival was 13.0+ months (range 4.0/16.2+). Over a total of 76 cycles (a mean of 3.1 cycles/patient), grade 1-2 leukopenia was seen in 9 patients (37%), grade 1-2 thrombocytopenia in 4 patients (17%), and grade 1 anemia in only 2 cases (8%). Grade 3 leukopenia was seen in 3 cases (12.5%). Grade 4 leukopenia or grade 3-4 thrombocytopenia were not seen. Gastrointestinal toxicity was very mild. CONCLUSIONS: Single agent gemcitabine at the dose of 1000 mg/m2 on a weekly schedule is active, at least in terms of objective response rate and tumor-related symptoms palliation, against pretreated urothelial carcinoma with good tolerability. These results compare favorably with those achieved with the most active drugs such as cisplatin and methotrexate.

Treatment of refractory metastatic breast cancer with 5-fluorouracil plus levofolinic acid as continuous venous infusion: a phase II study.

Effective palliation of metastatic breast carcinoma (MBC) after the failure of front-line chemotherapy for advanced disease, often based on the use of anthracyclines and taxanes, is quite difficult to achieve due to the development of dominant neoplastic cellular clones highly resistant to further therapy. Therefore the therapeutic index of second and third line chemotherapeutic treatments is usually quite low. Thirty patients with MBC with progressive disease after anthracycline-based chemotherapy as first line therapy were treated with l-FA 100 mg/m2/day and 5FU 1000 mg/m2/day ad continuous venous infusion for 96 hours every 4 weeks. Most patients (60%) had multiple sites of disease at entry and had visceral lesions as the dominant site of disease. Twenty-eight patients were evaluated for objective response: two patients had clinically progressive disease before restaging after the third cycle of chemotherapy. These patients were considered progressive disease since all patients were included in an intent-to-treat analysis. Nine patients achieved partial response for an overall response rate of 30% (intent-to-treat analysis) with a median duration of 9.5+ months (range 4.0/14.0 months), and disease stability was obtained in 10 cases (33%) with a median duration of 5.5 months (5-11). Progressive disease was recorded in 9 patients. After a median follow-up of 11 months, the overall median survival time of the whole series of patients was 14.0+ months. Objective responses were recorded both at visceral and bone sites. Chemotherapeutic treatment was generally quite well tolerated. No toxic deaths were recorded. Among gastrointestinal side-effects grade 3 stomatitis was noted in 30% of patients, and grade 3 diarrhea in 10% of cases. Grade 3-4 leukopenia was observed in 23% of patients, but significant episodes of febrile neutropenia were limited (2 patients). Grade 3 thrombocytopenia was seen only occasionally in 1 patient. Grade 1 anemia was recorded in 10% of patients. Hand-foot syndrome was noted in 2 patients (7%). Cardiotoxicity was minimal. The combination of 5FU and high-dose I-FA given as 96 hour continuous venous infusion was active, at least in terms of the overall response rate, against anthracycline refractory metastatic breast carcinoma. These results compare favourably with bolus 5FU/FA or other salvage regimens in terms of antineoplastic activity, and is well tolerated both subjectively and objectively by most patients.

Subcutaneous low-dose interleukin-2 and intravenous 5-fluorouracil plus high-dose levofolinic acid as salvage treatment for metastatic colorectal carcinoma.

Thirty-three consecutive patients with recurrent and/or metastatic colorectal carcinoma (CRC) refractory to previous chemotherapy have been treated with levofolinic acid (I-FA) 100 mg/m2 i.v. over 1 h infusion followed by 5-fluorouracil (5-FU) 600 mg/m2 i.v. bolus every week for 6 weeks followed by a 2 week interval. Patients also received rIL-2 s.c. at 3 MU daily from day 1 to day 5 of each week for at least four consecutive weeks per cycle. Enrolled patients were divided in two groups: (i) group 1 including patients with progressive tumor refractory to chemotherapy with I-FA + 5-FU given for metastatic disease and (ii) group 2 consisting of patients with diagnosis of metastatic disease within 3 months from the completion of adjuvant chemotherapy with 5-FU + levamisole (LEV) after primary surgery. No objective response was observed in the group of 11 patients with CRC resistant to previous I-FA + 5-FU, thus no further patient with progressive disease after I-FA + 5-FU was included in the trial. In the group of patients pretreated with 5-FU + LEV, four patients experienced a PR with a mean duration of 7.3 months (range > or = 4.0-8.6) for an overall response rate of 18% (95% CI 12-26%). A stabilization of disease was observed in five cases (23%) with a mean duration of > or = 5.6 months (range > or = 2.0-7.0). The remaining 13 patients progressed. No complete responses were achieved. The mean overall survival was > or = 9.5 months (range > or = 2.0-14.0). Toxicity was generally mild. This study demonstrates that the combination of s.c. rIL-2 and intravenous 5-FU + I-FA on a weekly schedule may be safely given to patients with metastatic CRC on an outpatients basis. The addition of low-dose rIL-2 does not modify the toxicity profile of 5-FU + I-FA, even if IL-2-related side-effects such as systemic symptoms or cardiac abnormalities are to be expected. The clinical activity of the combination is not good, at least in terms of response rate, even if the duration of partial responses may suggest to test rIL-2 in a prospective study with response duration and overall survival as the final end-points.

Usefulness of oral medroxyprogesterone acetate in the management of cancer-related cachexia-anorexia syndrome.

A study on the activity and tolerability of high-dose medroxyprogesterone acetate in the treatment of ACS in neoplastic patients was carried out in a series of 103 patients with advanced cancer beyond cure with standard chemotherapeutic or radiotherapeutic treatments. The treatment plan was: medroxyprogesterone acetate (MAP) 1,000 mg/day as liquid suspension orally at a single dose, for at least one month. If there was no improvement in body weight, SSA, performance status therapy was interrupted. An increase in body weight greater than or equal to 5%, in SSA score greater than or equal to 2 points, in performance status and then in quality of life were recorded as positive MAP-related events. Therapy-related toxicity was evaluated according to the WHO criteria. A mean body weight increased from 63 kg recorded before therapy to 67 kg recorded after 30 days of MAP. This difference was statistically significant (p<0.001). SSA increased from baseline value of 2.4 to 4.7, and mean performance status from 58.4 to 65. Again, these difference were highly significant (p<0.005 and p<0.001 respectively). The improvement in both mean body weight and SSA were statistically significant independent of performance status. Data presented in the present study confirm the clinical effectiveness of oral medroxy-progesterone acetate in the management of anorexia-cachexia syndrome in patients with advanced cancer resistant to systemic chemotherapy.

Second line chemotherapy for metastatic colorectal carcinoma.

25 patients with metastatic colorectal carcinoma previously treated with 5-fluorouracil and folinic acid for advanced disease, were treated with mitomycin C 8 mg/m(2) i.v. bolus on day 1, adriamycin 40 mg/m(2) i.v. bolus on day 1, and lonidamine 150 mg per os t.i.d. starting one day before chemotherapy and stopping 2 days after the end of chemotherapy. Treatment was repeated every 4 weeks. All patients had previous surgery and systemic chemotherapy with 5-fluorouracil and folinic acid given as first line chemotherapy for metastatic tumor. Sites of disease included liver, lung, nodes, abdomen, and bone. All enrolled patients were evaluable for objective response. Only one patient, affected by rectal carcinoma, showed a partial response (4%) which lasted 5.8+ months. No complete response was seen. Stable disease was recorded in 4 cases (16%) with a mean duration of 4.6+ months. All remaining patients had progressive disease. Median overall survival was 8.7+ months. Toxicity was significant. Grade 3 thrombocytopenia was seen in 8 cases (32%), and grade 3 leukopenia in 5 cases (20%). Grade 3 vomiting was observed in 9 patients (36%). The combination of mitomycin C, adriamycin and lonidamine is not effective in the treatment of metastatic colorectal adenocarcinoma resistant to 5-fluorouracil-based chemotherapy. These data suggest that lonidamine is not able to potentiate antineoplastic activity of chemotherapeutic drugs in humans and its use in colorectal cancer should be avoided since it has no or little impact on response rate and survival.

Oral granisetron with or without methylprednisolone versus metoclopramide plus methylprednisolone in the management of delayed nausea and vomiting induced by cisplatin-based chemotherapy. A prospective randomized trial.

BACKGROUND: A single-institution, randomized open trial was prospectively performed to compare orally administered granisetron with or without intramuscularly administered methylprednisolone to metoclopramide plus methylprednisolone in the prevention of delayed nausea and vomiting induced by cisplatin-based chemotherapy. The effects of antiemetic treatments were evaluated from days 2 to 5 of the first cycle after cisplatin administration among patients who had never before received chemotherapy. METHODS: All patients were treated with chemotherapeutic regimens containing cisplatin greater than or equal to 80 mg/m2 and received antiemetic therapy with granisetron 3 mg intravenously for the control of acute emesis. Patients who responded to treatment during the first 24 hours were randomized to receive (1) metoclopramide (0.5 mg/kg) intramuscularly three times daily plus methylprednisolone (125 mg) intramuscularly once a day or (2) granisetron (1 mg) orally twice daily or (3) oral granisetron (1 mg) orally plus methylprednisolone (125 mg) intramuscularly from days 2 to 5. RESULTS: Of the patients treated with metoclopramide plus methylprednisolone (n = 92), 53% had complete protection from delayed emesis, 16% a major response, 15% a minor response, and 15% no response. Of the patients treated with granisetron alone (n = 84), 33% had a complete response, 21% a major response, 23% a minor response, and 21% no response. In the patients treated with orally administered granisetron plus intramuscularly administered methylprednisolone (n = 86), 47% had a complete response, 17% a major response, 23% a minor response, and 13% no response. These differences reached statistical significance only when the complete response rate achieved in the metoclopramide plus methylprednisolone group was compared with that recorded in the oral granisetron group (P = 0.012). Moreover, the metoclopramide plus methylprednisolone and the orally administered granisetron plus corticosteroid arms were superior to the orally administered granisetron alone arm in preventing nausea (P < 0.038 and P < 0.002, respectively). No extrapyramidal side effects were noted for the granisetron alone and the granisetron plus methylprednisolone arms, whereas 6% of patients treated with metoclopramide had extrapyramidal adverse effects. Headache was recorded in 8% of patients treated with granisetron alone, in 9% treated with granisetron plus methylprednisolone, and in 3% treated with metoclopramide plus methylprednisolone. CONCLUSIONS: These data suggest that orally administered granisetron with or without methylprednisolone may be given safely to patients with cancer as prophylactic therapy against delayed emesis after high dose cisplatin therapy. Orally administered granisetron alone was less active than a standard combination of metoclopramide plus methylprednisolone. However, the addition of corticosteroid to orally administered granisetron improved the control of delayed emesis. The efficacy of the combination of metoclopramide plus methylprednisolone and oral granisetron with or without methylprednisolone against delayed emesis still is not entirely satisfactory.

Cisplatin plus vp16 as salvage treatment for advanced breast-carcinoma resistant or recurrent after 1st line chemotherapy for metastatic disease.

Forty patients with chemotherapy refractory metastatic breast carcinoma were enrolled in a phase II study of cisplatin 80 mg/m2 on day 1 plus VP16 100 mg/m2 on days 1-3 every 28 days. The overall response rate was 32% (95% CL 17-47%), with 2 patients (5%) showing a CR with a mean duration of 11.3 months, and 11 patients (27%) a PR with a mean duration of 7.8+ months. Seven patients (17%) had stable disease, and 20 patients (50%) progressed despite chemotherapy. One complete response and 4 partial responses were obtained in patients previously untreated with antracyclines. The overall survival was 10.2+ months. The mean survival of responding patients (CR+PR) was 15.5+ months, while that of non responders (NC+PD) was 8.6+ months. A total of 188 cycles were administered (4.7 cycles/patient) and the most frequent toxicities were gastrointestinal and hematological side-effects. The most severe toxicities were intense vomiting and anemia. Grade 3 vomiting was seen in 11 patients (27%), and grade 1-2 anemia in 30% of cases. Severe grade 3 leukopenia was seen in only 12% of cases. Mild renal toxicity was recorded only in 2 cases, while alopecia was observed in almost all patients. In conclusion, although CDDP plus VP16 regimen, may be safely given on an outpatient basis, its routine use as salvage treatment for chemotherapy refractory metastatic breast carcinoma is not recommended. This regimen may, however, be employed as second line chemotherapy in selected cases.

Cholesterol distribution between HDL subfractions. A study of 498 subjects.

In 498 subjects (205 normolipidemics and 293 hyperlipidemics) of both sexes, the cholesterol content of high density lipoprotein (HDL) subfractions has been determined. The serum concentration of total HDL-cholesterol appears to be more strictly related to the cholesterol content of HDL2 than to that of HDL3. This latter one, however, gives a contribution to the variability of HDL-cholesterol so that the value of HDL-cholesterol cannot be assumed as a reliable estimate of the serum level of the more anti-atherogenic HDL2 subfraction. The cholesterol content of HDL and its subfractions is higher in women than in men and decreases with increasing serum VLDL-cholesterol level and body weight. Both HDL2- and HDL3-cholesterol appear to largely depend from the metabolism of triglyceride-rich lipoproteins in accordance with the data of experimental studies.

Relationship of serum triglyceride concentration to lipoprotein composition and concentration in normolipidemic and hyperlipidemic subjects.

In a series of 438 subjects (184 normolipidemics and 254 hyperlipidemics) the relationship among serum concentration of triglycerides, lipoprotein lipids and apoproteins A-I and B has been evaluated. The results show that as serum triglyceride level increases, VLDL rise and become enriched in triglycerides. The increase of VLDL is associated with a reduction of serum levels of LDL and HDL which appear to be rich in triglycerides and poor in cholesterol. The decrease in serum HDL level is mainly due to a reduction in serum concentration of the HDL2 subfraction. The triglyceride content of HDL2 and HDL3 rises with increasing serum triglycerides. The increase in serum triglyceride concentration seems then to be associated with a complex metabolic derangement which involves all the lipoprotein fractions.

Probucol and cholestyramine combination in the treatment of severe hypercholesterolemia.

This study was carried out to evaluate the effect of the combined probucol and cholestyramine treatment on the lipoprotein pattern of hypercholesterolemic patients. Probucol was given in the dose of 1 g and cholestyramine in the dose of 16 g per day in 3 different sequences: Probucol, Cholestyramine, Probucol + Cholestyramine; Probucol + Cholestyramine, Probucol, Cholestyramine; Cholestyramine, Probucol + Cholestyramine, Probucol. After a period of dietary stabilization, 12 patients were randomly allocated to one of the treatment sequences to be followed for 9 months. Each treatment period lasted 3 months. During the cholestyramine period serum cholesterol decreased on the average by 18% and LDL cholesterol by 26%; during probucol, the mean decrease was 13% and 14%, and during the combined therapy 26% and 32%, respectively. Serum triglycerides and VLDL cholesterol showed a trend toward an increase during the cholestyramine period. HDL2 cholesterol significantly decreased during probucol treatment. Variation in both VLDL and HDL2 cholesterol observed when the drugs were given singly were no longer seen during the combination therapy.

Interrelationships between body mass and lipid and lipoprotein triglycerides and cholesterol in obese women.

In 72 obese women body mass index positively correlated with age and both showed multiple correlations with serum lipids and lipoprotein lipids. After adjustment for age (partial correlation procedure), body mass index resulted to be positively correlated with serum triglycerides, VLDL lipids, HDL-triglycerides and negatively correlated with HDL-cholesterol. The decrease in HDL-cholesterol concentration along with the increase in body weight was due to the reduction of cholesterol in HDL2 subfraction, while HDL3-cholesterol did not show any significant correlation with body mass index. The negative correlation between HDL2-cholesterol and body mass index was independent of other lipoprotein variables and in particular of VLDL lipid levels that were, as expected, inversely related to HDL2-cholesterol. HDL2-cholesterol is believed to be a strong protective factor against atherosclerosis, while doubts exist on the meaning of VLDL lipids as risk factors. Thus, the decrease in HDL2-cholesterol concentration, rather than the increase in VLDL lipids, might give a rational basis to the high incidence rate of vascular disease in obese subjects.

Long-term effects of bezafibrate and of a bezafibrate and cholestyramine combination on lipids and lipoprotein lipids in type IIa hypercholesterolaemic patients.

Eighteen hypercholesterolaemic patients have been treated for four months with bezafibrate 200 mg thrice daily. After one month of therapy, total cholesterol (T-C) decreased on the average by 19%, total triglycerides (T-TG) by 28%, very low density lipoprotein-TG by 47%, LDL-C by 25% and HDL3-C increased by 16%. At the fourth month of therapy the lipoprotein pattern was unchanged as compared to the one observed at the first month. In 12 patients T-C was normalized by bezafibrate and the patients continued the treatment for one year without experiencing further changes in lipoprotein pattern. Six patients with severe hypercholesterolaemia (mean baseline T-C of 11.51 +/- 0.63 mmoles/l) failed to adequately respond to bezafibrate treatment and were put on the combined bezafibrate 600 mg/day and cholestyramine 16g/day therapy. During bezafibrate their T-C decreased on the average by 21% and LDL-C by 23% and during the combined therapy by 33% and by 37% respectively, as compared to the baseline values. Combined bezafibrate and cholestyramine treatment seems then to be more effective than bezafibrate alone in decreasing serum cholesterol and may be useful in patients with severe hypercholesterolaemia.

Changes in serum lipoprotein pattern following bezafibrate. Differential effects in type IIa and in type IIb hyperlipoproteinemic patients.

Sixteen type IIb and 26 type IIa hyperlipoproteinemic patients were treated with bezafibrate 200 mg t.i.d. After 1 month VLDL-TG decreased by 54% in type IIb and by 43% in type IIa; LDL-C decreased by 13% in type IIb and by 23% in type IIa patients. HDL3-C rose in both group of patients, while HDL2-C significantly increased (52%) only in patients with phenotype IIb. The change in LDL-C and in HDL2-C concentrations resulted to be related to the pretreatment VLDL lipid concentration and to its change during the treatment. Twenty patients were treated with bezafibrate for 4 months. On the average, the changes in lipoprotein lipid concentration attained at the end of the first month of therapy remained substantially constant in the following 3 months.

Changes in the serum lipoprotein pattern induced by two low-fat diets with a different vegetable content in hypercholesterolemic patients.

Thirty-two hypercholesterolemic outpatients were treated by a conventional low-fat diet (carbohydrate 56%; fat 25%; vegetable proteins 7%; animal proteins 12% of energy; P/S ratio 1.0). After 1 month T-C decreased by 11%, VLDL-C by 32%, LDL-C by 8%, HDLt-C by 10% and HDL2-C by 11%. Thirty-two comparable patients were treated by a different low-fat diet which provided 69% of energy as carbohydrate, 19% as fat, 7% as vegetable proteins and 5% as animal proteins; P/S ratio was 1.3. After 1 month T-C decreased by 9% and LDL-C by 12%. VLDL-C, HDL2-C and HDL3-C did not change significantly. A cross-over study on 24 patients confirmed that both diets have lowering effects on T-C and LDL-C levels, but only the conventional low-fat diet decreases VLDL-C and HDL2-C.

Serum lipoprotein subfractions before and during low-calorie diet in obese women.

Twenty-five obese women were put on low-calorie diet for one month. The mean weight loss was 2.7 kg and was accompanied by a 9% decrease of LDL-cholesterol. LDL-apolipoprotein B (in 13 subjects) showed a 16% fall and LDL-triglyceride levels did not change. The results suggest both a decrease of LDL concentration and a relative increase of triglyceride-rich particles in the density range of 1.006-1.063. HDL2-cholesterol showed a 17% decrease and HDL3-cholesterol a 16% increase. Total and lipoprotein triglycerides were not modified. The changes of lipoprotein pattern suggest a sluggish VLDL catabolism by lipoprotein lipase. In 10 women followed for 6 months the decrease of LDL-cholesterol seen after one month of diet was no more present at the 6th month, while the decrease of HDL2-cholesterol and the increase of HDL3-cholesterol were still evident. At the end of the 6th month a slight but significant decrease of total and VLDL-triglycerides also occurred.