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Biomedical subjects

F Cavalli

Publications and source records attributed to F Cavalli.

At least 181 records · Page 10Linked to original sources
PubMed1988

Lack of effect of cisplatin on i.v. L-PAM plasma pharmacokinetics in ovarian cancer patients.

Melphalan (L-PAM) pharmacokinetics were investigated in nine ovarian cancer patients before and after cisplatin (DDP) treatment. When L-PAM was given 24 h before DDP, the elimination half-life (t 1/2 beta), plasma clearance (Clp), and volume of distribution (Vd beta) of L-PAM were, respectively: 46.4 +/- 6.7 min, 20.5 +/- 3.7 l/m2, and 306.8 +/- 34.4 ml/min per square meter. When L-PAM was inoculated 24 h after DDP, t 1/2 beta, Clp, and Vd beta were 47.5 +/- 6.3 min, 20.4 +/- 2.8 l/m2, and 322.0 +/- 54.1 ml/min per square meter. Thus, DDP pretreatment does not significantly affect L-PAM pharmacokinetics. Regression analysis showed a significant correlation between the L-PAM elimination rate constant (beta) and renal function assessed by creatinine clearance. One patient who received this sequence of treatment for six courses showed a threefold decrease of L-PAM Clp after the last treatment. The reported high myelotoxicity of the combination of DDP and L-PAM when DDP was given 24 h before L-PAM cannot be attributed to DDP-induced changes in L-PAM kinetics but might to some extent be related to a loss of renal function consequent to many courses of treatment.

Adult↗
PubMed1988

Iproplatin and carboplatin induced toxicities: overview of phase II clinical trial conducted by the EORTC Early Clinical Trials Cooperative Group (ECTG).

Data of five phase II clinical trials on iproplatin and carboplatin, conducted by the ECTG, have been pooled in order to evaluate the extent of toxicities of these compounds. One hundred and seventy patients treated with iproplatin and 65 patients treated with carboplatin were evaluable. Most of them (81%) had been previously treated with chemotherapy. Doses ranged from 180 to 300 mg/m2 every 4 weeks for iproplatin, and from 350 to 450 mg/m2 every 5 weeks for carboplatin, according to the initial status of the patient. WHO criteria were used to grade toxic effects. Weekly blood counts were performed, and lowest observed counts were analysed by non-parametric methods. Censored data were analysed by actuarial methods. Thrombocytopenia was the dose-limiting toxicity and was dose related. Leucopenia was less severe. The risk of thrombocytopenia varied largely amongst patients, and could be predicted from the initial platelet count, the initial creatinine level and prior therapy with alkylating agents. The cumulative risk increased with the total dose, but with a decreasing hazard rate, and without additional delay to platelet recovery. Nausea, vomiting and diarrhoea were the most frequently observed non-haematological side-effects, and were more severe with iproplatin than with carboplatin. Peripheral neuropathy was observed in some cases, but could be due to prior treatments. Renal toxicity did not cause major problems. Our results confirm the findings of the phase I trials: thrombocytopenia is dose-limiting for both drugs, and renal side-effects are negligible. The risk model of thrombocytopenia, consistent with Egorin's model for carboplatin, could serve as a basis for dose adjustment. The feasibility of the scheme could be insufficient for prolonged treatment.

Adult↗
PubMed1988

Phase I study of the antifolate N10-propargyl-5,8-dideazafolic acid, CB 3717.

The thymidylate synthase (TS) inhibitor CB 3717 was administered intravenously to 24 adult patients as a single bolus repeated every 3-4 weeks. The doses were escalated from 50 to 400 mg/m2. At the highest level, hydration and urinary alkalinization were routinely performed. A greater than 20% decrease of the creatinine clearance value occurred in 35% of the cycles performed at 400 mg/m2, a dose which could be recommended for phase II studies. Hepatic toxicity, represented by an increase of the glutamic pyruvic transaminase (GPT) plasma levels, occurred in 70% of the patients after the first cycle. GPT peak levels were neither related to the dose nor to the peak drug plasma concentrations or AUC values in the dose range from 225 to 400 mg/m2. Malaise, reported after 46% of the cycles, was the most disturbing side-effect and its occurrence was statistically correlated with the degree of elevation of GPT. A suggestion of antitumor activity was reported for dosages of 300 and 400 mg/m2 in three patients with ovarian cancer refractory to cisplatin. Further clinical evaluations of TS inhibitors rely on the development of more water soluble and less hepato- and nephrotoxic agents.

Adult↗
PubMed1988

A randomized comparison of doxifluridine and fluorouracil in colorectal carcinoma.

In a randomized study 52 patients with advanced colorectal cancer and measurable lesions were treated with doxifluridine 4000 mg/m2 or fluorouracil 450 mg/m2 i.v. on 5 consecutive days over 3 weeks. None had prior fluoropyrimidines except two who received adjuvant fluorouracil. Partial responses with a duration ranging from 259 to 406 days were observed in five patients treated with doxifluridine and two patients treated with fluorouracil. Toxic reactions were evaluated in 88 doxifluridine courses and 105 fluorouracil courses. The most frequent adverse effects were neurotoxicity (48% of patients) and mucositis (43%) for doxifluridine, leukopenia (48%) and nausea/emesis (37%) for fluorouracil. Mucositis, diarrhea, nausea, emesis and skin reactions were observed in both treatment groups. Fluorouracil produced neurotoxic effects in 26% of patients. Reversible cardiac dysfunctions were observed in four patients treated with doxifluridine, expressed by ectopic ventricular beats (2) precordial pains (1) and ventricular fibrillation (1). This latter toxicity justified the premature interruption of the study. Doxifluridine is an active agent in colorectal cancer. Compared to fluorouracil it produces, when used i.v., a lower myelosuppression and a greater incidence of neurological and cardiac toxicity.

Adenocarcinoma↗
PubMed1988

Phase II study of iproplatin in advanced ovarian carcinoma.

Iproplatin (cis-dichloro-trans dihydroxy-bis-isopropyl-amine platinum [IV]; CHIP) was administered intravenously (IV) at monthly intervals at doses of 300 mg/m2 and 240 mg/m2 to ten previously untreated and 97 previously treated patients with advanced ovarian carcinoma. The overall response rate was 78% among patients with no prior chemotherapy, 42% among patients with prior chemotherapy not including cisplatin, and 22% among patients with prior chemotherapy including cisplatin. Overall response rates to iproplatin were 6.4% and 54% in patients with/without clinical evidence of tumor resistance to cisplatin. Thrombocytopenia was the dose-limiting toxicity, median time to nadir and to recovery being 2 and 4 weeks, respectively. Patients who had received prior chemotherapy regimens for greater than 1 year showed a 10% greater reduction in platelet count (mean platelet nadir +/- SD, 57.5 +/- 49.96 X 10(3)/microL) and a higher incidence of grade 3 to 4 thrombocytopenia after the first cycle than patients who had received prior chemotherapy regimens for less than 1 year (94.7 +/- 65.99 X 10(3)/microL) Moderate to severe vomiting and diarrhea occurred in 84% and 16% of patients pretreated with chemotherapy. Neuropathy (6%) was reported only in patients with prior cisplatin treatment. Mild and reversible renal toxicity was observed in 6% of cases. Iproplatin is an active drug in ovarian cancer; the results achieved in patients previously treated with cisplatin strongly suggest that the two drugs are cross-resistant.

Antineoplastic Agents↗
PubMed1987

Enzymuria in carboplatin nephrotoxicity.

Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) is an early marker of nephrotoxicity. NAG activity was assayed by the fluorimetric method of Leaback and Walker in 17 patients treated (22 courses) with carboplatin (CBDCA, 220-550 mg/m2) before infusion and 24, 48, 72 and 96 h after. Increased excretion of NAG, a sensitive index of renal tubular damage, was observed following 10 of the 22 courses. A transient increase in plasma creatinine and/or abnormal proteinuria was observed in 6 cases. Impaired renal function prior to therapy seems to be a predisposing factor to the nephrotoxicity.

Acetylglucosaminidase↗
PubMed1987

A randomized study of methotrexate, bleomycin, hydroxyurea with versus without cisplatin in patients with previously untreated and recurrent squamous cell carcinoma of the head and neck.

The value of a combination of methotrexate, bleomycin and hydroxyurea with vs. without cisplatin was randomly examined in 62 evaluable patients with previously untreated (44 patients) and recurrent (18 patients) squamous cell carcinoma of the head and neck. Methotrexate (30 mg/m2) and bleomycin (15 mg) were given intravenously weekly, hydroxyurea (1000 mg/m2) per os 3 times per week for 4 weeks. Cisplatin (60 mg/m2) was added on Day 1 every month. A higher overall response rate was observed with the cisplatin-containing regimen (66%, included 17% complete) as compared with 27% (3% complete) with the 3-drug combination (P value 0.0025). The cisplatin-containing regimen was more active in both previously untreated patient group and in the group recurrent patients. Toxicity was more pronounced in the cisplatin regimen and necessitated frequently reduced drug dosages. No survival difference was observed between the treatment groups. Median survival in previously untreated patients was 16.2 months and 7.2 months in patients who failed conventional local treatment. It is concluded that a cisplatin-containing regimen is more effective in advanced head and neck carcinoma than the same combination without cisplatin.

Adult↗
PubMed1987

Effects of pK variability on bicarbonate balance evaluation in dialysis patients.

Bicarbonate balance is usually calculated from the Henderson-Hasselbalch equation under the assumption that pK is constant. To evaluate the pK variability and its effects on bicarbonate computed with autoanalyzers in dialysis patients, we studied 44 patients on maintenance hemodialysis. The pH, PCO2, total CO2, and pK were determined in each patient before and after the dialysis session. The mean total CO2 calculated (22.5 +/- 2.7 meq/L) from pH and PCO2 values was significantly higher (p less than 0.001) than that directly measured (20.4 +/- 3.0 meq/L) with total CO2 analyzer. The mean (+/- SD) pK value was 6.14 +/- 0.06 (range 6.05-6.28). The percentage error in computed bicarbonate due to pK variations from the traditional pK value of 6.1 ranged between -11% and 52%. The pK value changed during dialysis in the majority of our patients, thereby confirming that pK consistency does indeed vary. Thus, investigation of acid-base balance based on pH and PCO2 determination may lead to erroneous results determined by pK abnormalities.

Acid-Base Equilibrium↗
PubMed1987

Complete remission following endocrine or combined cytotoxic and hormonal treatment in advanced breast cancer. A retrospective analysis.

Among 422 patients with advanced breast cancer treated in a randomized trial we observed 60 complete responses (CR). Sixteen were achieved among 206 patients treated with endocrine therapy alone and 37 among 216 patients treated with concomitant chemotherapy and endocrine therapy. The incidence of CR in women treated with the concomitant modality was higher in those with dominant soft tissue disease, intermediate in those with osseous or pulmonary involvement, and low in patients with liver metastases. Bone was shown to be the organ most responsive to therapy among patients treated with hormonotherapy, while patients with soft tissue metastases had an unexpectedly low rate of complete remission with this modality. The probability of achieving a CR was inversely proportional to the tumor burden in the patients treated with concomitant chemotherapy and endocrine therapy. For complete responders on hormone treatment alone and for those on combined endocrine and cytotoxic therapy, both median time to progression (26 and 29 months, respectively) and survival (52 and 53 months, respectively) were similar and statistically significantly longer than in partial or minor responders. This observation leads us to the conclusion that the hormonal component is the determinant for the length of a CR.

Actuarial Analysis↗
PubMed1987

[Prostaglandin E2 liberation in the synovial fluid induced by organo-iodinated contrast media. Interrelations with the genesis of post-arthrographic pain].

RCM have been observed to cause--during arthrography--the appearance of a slow onset painful symptomatology with the clinical characteristics of a slight and transient acute arthritis. These substances are supposed to set in a production of humoral mediators of inflammation with algogenic action--PGE2 in particular. During arthrography of the knee the release of synovial fluid PGE2 after RCM introduction was studied. Two RCM were compared: meglumine iothalamate and iopamidol. Twenty patients underwent arthrography of the knee: synovial fluid PGE2 concentration was measured both before and 15' after RCM introduction with 125I-RIA method. Results show a significant increase in PGE2 concentration after both iothalamate (p less than 0.0001) and iopamidol (p less than 0.01) --especially in iothalamate--treated patients (p less than 0.01). A physiopathologic mechanism about post-arthrographic pain and, more generally, about RCM toxicity is thus hypothesized.

Arthrography↗