Drug survival, effectiveness and safety of ixekizumab for moderate-to-severe psoriasis up to 5 years.

INTRODUCTION: Ixekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real-life studies. Nevertheless, long-term real-world experiences are still lacking, with little data up to 4 years of treatment. OBJECTIVES: To analyse survival, effectiveness and safety of ixekizumab in a real-life cohort of patients affected by moderate-to-severe psoriasis or psoriatic arthritis up to 260 weeks (5 years). METHODS: We included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and ≤3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response. RESULTS: DS was 65.5% at 260 weeks, with being a super-responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and ≤3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87-0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84-0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88-0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83-0.99, p = 0.027), and PASI ≤3 (OR 0.86, CI 0.76-0.97, p = 0.018) at 104 weeks. No severe adverse events were observed. CONCLUSIONS: Ixekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long-term response.

[Ductal carcinoma in situ: role of the boost]. / Radiothérapie des carcinomes canalaires in situ: impact du complément d'irradiation du lit tumoral.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

A prospective randomized study comparing high- and low-dose leucovorin combined with same-dose 5-fluorouracil in advanced colorectal cancer.

Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well established for advanced colorectal cancer, the question of the most effective regimen and optimal dose of leucovorin remains unanswered. This prospective randomized trial compares low-dose (group 1) and high-dose (group 2) leucovorin, combined with the same dose of 5-FU to determine whether high-dose leucovorin was more beneficial than low-dose on overall survival. Inclusion criteria were: unresectable metastatic colorectal carcinoma, with or without evaluable tumor response; a performance status of less than grade 3 (World Health Organization classification); and no previous chemotherapy for metastases. Forty-two patients were randomized in group 1 (leucovorin, 20 mg/m2/day, days 1 through 5) and 41 patients in group 2 (leucovorin, 200 mg/m2/day, days 1-5). All the patients in the two groups received a 1-hour infusion of 400 mg/m2/day 5-FU every 4 weeks. The two groups were matched with no statistically significant differences in gender ratio, site of primary tumor, performance status, and tumor extent. Toxicity in the two regimens was low and not significantly different between the two groups. Overall median survival was 346 days in group 1 and 323 days in group 2 and was not significantly different between the two groups. At 1 year, the test of equivalence was significant (p < 0.01), demonstrating an absence of more than 20% benefit in 1-year survival for the high-dose regimen. The use of high-dose leucovorin combined with 5-FU in the 5-day regimen does not significantly improve overall survival for patients who have metastatic colorectal cancer.

[Carboplatin and urothelial tumors: review of the literature]. / Le carboplatine et les tumeurs urothéliales: revue de la littérature.

Polychemotherapy appears to increase survival moderately but at a cost of severe toxicity, mainly due to cisplatin. New platinum salts (chiefly carboplatin) have therefore been developed. This review on the use of carboplatin in advanced-stage urothelial tumours was undertaken to find the actual place of carboplatin in the treatment of these tumours, and to describe its best use in polychemotherapy. In 322 patients, carboplatin alone gave 12.9% objective responses (OR), 2.5% complete responses (CR) and 10.4% partial response (PR). Many polychemotherapy protocols were used, most frequently carboplatin/methotrexate/vinblastin. The results were OR: 63%, CR: 19%, PR: 44% among 146 patients. These results confirm the relative efficiency of carboplatin on urothelial tumours, particularly when used in combination. Because of the lack of prospective studies and the wide disparity in the doses and in the dose adjustment, no comparison can be made with cisplatin. Carboplatin has virtually no renal toxicity at the usual doses, and does not require hyperhydratation. The pharmacokinetic behaviour of the two platinum salts is highly different, as carboplatin does not undergo tubular metabolism. The efficiency and tolerance of carboplatin used to be optimised by adapting the dose to the glomerular filtration rate, as was shown for germ cell tumours. In conclusion, these considerations fully warrant further clinical trials of carboplatin.

Carboplatin and urothelial tumors.

The prognosis of advanced-stage bladder cancer is poor. Chemotherapy, particularly regimens including platinum salts, appears to increase survival moderately but at the cost of severe, mainly renal toxicity. Platinum is a major factor in this toxicity, and new platinum salts (chiefly carboplatin) have therefore been developed. Carboplatin has no renal toxicity at usual doses, and its use does not require concomitant hyperhydration. Its gastrointestinal, otologic, and general tolerability is excellent. In contrast, most patients develop thrombocytopenia, which can be important, but which is always transitory. The platelet count reaches its nadir (grade 2 or 3) at around day 20, and the leukocyte nadir (grade 2 or 3) occurs about day 19. Anemia is rare. The literature on the use of carboplatin for the treatment of advanced-stage urothelial tumors is reviewed. Carboplatin is used at doses varying between 200 and 400 mg/m2, administered in 28-day courses. Dose adjustment is based on serum creatinine level, creatinine clearance, nadir blood cell levels, or previous treatment, reflecting the wide disparity between different studies. Used alone, carboplatin achieved objective responses (ORs) in 14% of patients (3% complete responses, CRs, and 11% partial responses, PRs) in a total group of 327 patients included in 13 trials. In polychemotherapy various combinations of carboplatin with other agents have been reported, most frequently carboplatin/methotrexate/vinblastine; the OR rate was 63% (CR rate 19% and PR rate 44%) among 88 patients in four studies. These results confirm the relative efficacy of carboplatin in the treatment of advanced-stage urothelial tumors, particularly when it is combined with other agents. Its efficacy is similar to that of cisplatin, but it is far less toxic. A prospective, comparative trial will be necessary to confirm these data. The pharmacokinetic behaviors of the two platinum salts are markedly different, as carboplatin does not undergo tubular metabolism. The efficacy of carboplatin could be optimized by adapting the dosage to the glomerular filtration rate, which is a more accurate method than extrapolation from the serum creatinine or creatinine clearance values. This has been shown in the case of nonseminomatous germ cell tumors. Calculation of the optimum carboplatin dose should now be applied to urothelial tumors. The general and renal tolerability of a platinum salt is an important element of choice when the efficacies are equivalent. These considerations fully warrant further clinical trials of carboplatin.