Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08–2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08–2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26–2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy

Invasive mechanical ventilation in cancer patients: prior non-invasive ventilation is a poor prognostic factor

info:eu-repo/semantics/publishe

Rilpivirine use in the Swiss HIV cohort study: a prospective cohort study.

Rilpivirine is safe and effective in HIV-naïve patients with low baseline HIV-RNA or in switch strategy. It offers the advantages of few drug-drug interactions and a favourable toxicity profile. We aimed to determine the reasons for prescribing the rilpivirine (RPV)/tenofovir disoproxil (TDF)/emtricitabine (FTC) co-formulation within the Swiss HIV Cohort Study and to assess its effectiveness and safety over a 24 months period. All individuals enrolled in the Swiss HIV Cohort Study who initiated a RPV/TDF/FTC co-formulation between April 2013 and March 2014 were included. Primary outcomes were the HIV-RNA viral load (copies/mL) and CD4 cell count (cells/mm(3)) at 6, 12 and 24 months. Reasons for a switch to RPV/TDF/FTC were evaluated through a standardized questionnaire. We also assessed discontinuation and reasons for discontinuation of RPV/TDF/FTC until October 30, 2015. Of 644 individuals who started the RPV/TDF/FTC co-formulation, only 7.5% were treatment-naïve. At 24 months, viral suppression (HIV-RNA <50 copies/mL) was achieved in 100% and 96.7% of cART-naïve and cART-experienced patients respectively. The switch to RPV was mainly done for simplification (44.6%) and to overcome central nervous system toxicity symptoms due to efavirenz (24%). Six months after switch, 74.8% of patients reported an improvement of psycho-neurological symptoms with continued improvement at 12 months for almost 80%. However, one quarter of patients reported a discontinuation of RPV/TDF/FTC on October 30, 2015 after a median time of 18.4 months. Reasons for discontinuation included physician decision (5.3%) and side-effects (3.9%) mainly related to the central nervous system and to renal toxicity. The RPV/TDF/FTC co-formulation was safe and effective throughout 24 months of follow-up but barely prescribed for HIV-naïve patients. Despite excellent virological suppression among both treatment-naïve and -experienced patients, we observed a high rate of treatment discontinuation

Stable HIV-1 reservoirs on dolutegravir maintenance monotherapy: the MONODO study.

Dolutegravir (DTG) is a highly effective integrase inhibitor with a strong genetic resistance barrier and a potential role in simplified HIV maintenance treatment. We assessed the feasibility of DTG maintenance monotherapy and measured HIV reservoirs on DTG monotherapy. An interventional, open-label, single-arm study including eight virologically suppressed HIV-1-infected patients switched to DTG 50 mg once daily for 24 weeks was performed. HIV-1 RNA levels in plasma and cerebrospinal and seminal fluids were measured at baseline and week 24, as well as HIV-1 DNA in peripheral cells and DTG concentrations in these compartments. HIV-1 RNA remained undetectable in all samples of blood, cerebrospinal fluid and sperm throughout the 24 weeks, except for one cerebrospinal fluid sample with a value of 28 HIV-1 RNA copies/mL at week 24. One patient discontinued the study because of a neurological side effect. There was no change in the mean HIV-1 DNA level between baseline and week 24. Plasma and cerebrospinal fluid DTG concentrations reached therapeutic levels in all patients in these two compartments. In this small sample of carefully selected patients, HIV-1 reservoirs were well controlled on DTG monotherapy over a period of 24 weeks. Viral suppression was also maintained throughout follow-up

A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer

IntroductionIn a literature meta-analysis, we showed survival benefits for regimens including cisplatin [hazard ratio (HR) 0.61; 95% confidence interval (CI), 0.57–0.66] and for those including etoposide (HR 0.65; 0.61–0.69). That benefit was mainly observed when etoposide alone or in combination with cisplatin was included in the chemotherapy regimens. Our objective was to determine if chemotherapy with both drugs improves survival in comparison to a non-platinum regimen with etoposide.MethodsExtensive small-cell lung cancer patients were randomized between cisplatin–etoposide (CE) and ifosfamide + etoposide + epirubicin regimen (IVE) between 2000 and 2013.Results176 and 170 eligible patients were allocated to CE and IVE (315 deaths were required before analysis), respectively. Objective response rates were not significantly different: 60% with CE and 59% with IVE. No statistically significant difference in median survival and 1-year and 2-year was observed with rates of 9.6 months, 31 and 5% for CE and 10 months, 39 and 9% for IVE, respectively. HR was 0.84 (95% CI 0.68–1.05, p = 0.16). Only two prognostic factors for survival were retained in multivariate analysis: sex with HR = 0.69 (95% CI 0.49–0.97, p = 0.03) and performance status with HR = 0.53 (95% CI 0.49–0.97, p < 0.0001). After adjustment for these prognostic factors, HR for survival was 0.83 (95% CI 0.65–1.08, p = 0.17). There was more thrombopenia in the CE regimen and more leukopenia with IVE.ConclusionCombination of CE failed to improve survival in comparison to an etoposide-containing regimen without cisplatin.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT00658580?term=ELCWP+01994&rank=1, identifier NCT00658580

Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer

A phase III randomized trial was conducted in patients with metastatic NSCLC, to determine if, in association with mitomycin (6 mg m–2) and ifosfamide (3 g m–2), the combination of moderate dosages of cisplatin (60 mg m–2) and carboplatin (200 mg m–2) – CarboMIP regimen – improved survival in comparison with cisplatin (50 mg m–2) alone – MIP regimen. A total of 305 patients with no prior chemotherapy were randomized, including 297 patients assessable for survival (147 in the MIP arm and 150 in the CarboMIP arm) and 268 patients assessable for response to chemotherapy. All but eight (with malignant pleural effusion) had stage IV disease. There was a 27% (95% CI, 19–34) objective response (OR) rate to MIP (25% of the eligible patients) and a 33% (95% CI, 24–41) OR rate to CarboMIP (29% of the eligible patients). This difference was not statistically significant (P = 0.34). Duration of response was not significantly different between both arms. There was also no difference (P = 0.67) in survival: median survival times were 28 weeks (95% Cl, 24–32) for MIP and 32 weeks (95% Cl, 26–35) for CarboMIP, with respectively 1-year survival rates of 24% and 23% and 2-year survival rates of 5% and 2%. The main toxicities consisted in emesis, alopecia, leucopenia and thrombocytopenia, that were, except alopecia, significantly more severe in the CarboMIP arm. Our trial failed to demonstrate a significant improvement in response or survival when patients with metastatic NSCLC were treated, in addition to ifosfamide and mitomycin, by combination of moderate dosages of cisplatin and carboplatin instead of moderate dosage of cisplatin alone. The results support the use of a moderate dose (50 mg m–2) of cisplatin in combination with ifosfamide and mitomycin for the chemotherapy of this disease. © 2000 Cancer Research Campaig

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis [version 2; peer review: 3 approved].

Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. : Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant's median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/µl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis [version 1; referees: 3 approved]

Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results: Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant’s median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/µl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART