Abstract Background In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue ( KRAS ) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX ...folinic acid, 5-fluorouracil, and oxaliplatin or FOLFIRI folinic acid, 5-fluorouracil, and irinotecan. However no trial has directly compared these combinations. Methods Multicentre, open-label study in untreated patients ≥ 18 years with (WT)- KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 + R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT- RAS patients. Results Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WT- RAS : 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab-FOLFIRI (WT- RAS : 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT- RAS : 37%/69%). The R0-R1 resection rate was 34%/46% (WT- RAS :26%/54%). Median PFS was 13/14 months (hazard ratio HR Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: 0.6–1.5; WT- RAS :13/15; HR: 0.7 0.4–1.3). Median OS was 37/41 months (HR:1.0 0.6–1.8; WT- RAS : 39/49; HR:0.9 0.4–1.9). In WT- RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS ≥ 30%/ ≥ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p = 0.003) and neuropathy (13%/0%; p = 0.025) in the Pmab-FOLFOX4 arm. Conclusions In patients with WT- KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (clinicaltrials.gov: NCT00885885 ).
Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The "Tratamiento de Tumores Digestivos" group (TTD) previously reported in a ...randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years.
Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks).
In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%).
the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term.
EudraCT number: 2009-010192-24 . Clinicaltrials.gov number: NCT01043484 .
Abstract Background Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining ...capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC. Patients and methods Previously untreated mPC patients were randomised to receive G (1000 mg/m2 , days 1, 8, 15) + E (100 mg/day, days 1–28) + C (1660 mg/m2 , days 1–21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety. Results 120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine–erlotinib–capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio HR: 0.88, 95% confidence interval CI: 0.58–1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72–1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26–0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33–0.77; p = 0.0014). Conclusion PFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy. The study was registered with ClinicalTrials.gov: NCT01303029.
We aimed to test the non-inferiority of oral versus intravenous hydration in the incidence of contrast-associated acute kidney injury (CA-AKI) in elderly outpatients undergoing a contrast-enhanced ...computed tomography (CE-CT) scan.
PNIC-Na (NCT03476460) is a phase-2, single-center, randomized, open-label, non-inferiority trial. We included outpatients undergoing a CE-CT scan, >65 years having at least one risk factor for CA-AKI, such as diabetes, heart failure, or an estimated glomerular filtration rate (eGFR) of 30-59 mL/min/1.73 m². Participants were randomized (1:1) to oral sodium-chloride capsules or intravenous hydration. The primary outcome was an increase in serum creatinine >0.3 mg/dL or a reduction in eGFR >25% within 48 h. The non-inferiority margin was set at 5%.
A total of 271 subjects (mean age 74 years, 66% male) were randomized, and 252 were considered for the main analysis (per-protocol). A total of 123 received oral hydration and 129 intravenous. CA-AKI occurred in 9 (3.6%) of 252 patients and 5/123 (4.1%) in the oral-hydration group vs. 4/129 (3.1%) in the intravenous-hydration group. The absolute difference between the groups was 1.0% (95% CI -4.8% to 7.0%), and the upper limit of the 95% CI exceeded the pre-established non-inferiority margin. No major safety concerns were observed.
The incidence of CA-AKI was lower than expected. Although both regimens showed similar incidences of CA-AKI, the non-inferiority was not shown.
Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal ...junction adenocarcinoma (GEJA). The addition of trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and we aimed to explore its role in the perioperative setting.
This Spanish, multicentre, open-label phase II trial evaluated the efficacy and toxicity of perioperative capecitabine, oxaliplatin and trastuzumab (XELOX-T) in patients with HER2-positive resectable GA or GEJA. The primary end-point was 18-months DFS; and secondary end-points included pathological complete response (pCR) rate, R0 resection rate, OS and toxicity (NCT01130337).
Thirty-six patients were included. After three cycles of preoperative treatment, 14 patients (38% of the intention-to-treat population) had partial response and 18 (50%) had stable disease. Surgery was performed in 31 patients: 28 (90%) had R0 resection, three (9.6%) had a pCR and three (9.6%) died due to surgical complications. A total of 24 patients received post-operative XELOX-T, 22 of whom completed trastuzumab maintenance. Main grade III/IV toxicities included diarrhoea (33%), nausea and vomiting (8%). After a median follow-up of 24.1 months, 18-month DFS was 71% (95% confidence interval CI, 53–83%); and an update after 102 months of follow-up showed a median OS of 79.9 months and a 60-month OS of 58% (95% CI, 40–73%).
These data suggest that perioperative XELOX-T in patients with HER2-positive GA and GEJA is feasible and active. Further investigation in randomised studies is warranted.
•Perioperative administration of XELOX-T is safe and tolerable.•Beyond expectation, 70% patients achieved a disease-free survival of 18 months.•This scheme should be further investigated in larger randomised clinical trial.
Perioperatory chemoradiotherapy (CRT) improves local control and survival in patients with locally advanced rectal cancer (LARC). The objective of the current study was to evaluate the addition of ...bevacizumab (BEV) to preoperative capecitabine (CAP)-based CRT in LARC, and to explore biomarkers for downstaging.
Patients (pts) were randomized to receive 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent CAP 825 mg/m(2) twice daily 5 days per week and BEV 5 mg/kg once every 2 weeks (3 doses) (arm A), or the same schedule without BEV (arm B). The primary end point was pathologic complete response (ypCR: ypT0N0).
Ninety pts were included in arm A (44) or arm B (46). Grade 3-4 treatment-related toxicity rates were 16% and 13%, respectively. All patients but one (arm A) proceeded to surgery. The ypCR rate was 16% in arm A and 11% in arm B (p =0.54). Fifty-nine percent vs 39% of pts achieved T-downstaging (arm A vs arm B; p =0.04). Serial samples for biomarker analyses were obtained for 50 out of 90 randomized pts (arm A/B: 22/28). Plasma angiopoietin-2 (Ang-2) levels decreased in arm A and increased in arm B (p <0.05 at all time points). Decrease in Ang-2 levels from baseline to day 57 was significantly associated with tumor downstaging (p =0.02).
The addition of BEV to CAP-based preoperative CRT has shown to be feasible in LARC. The association between decreasing Ang-2 levels and tumor downstaging should be further validated in customized studies.
Clinicaltrials.gov identifier NCT01043484. Trial registration date: 12/30/2009.
Purpose
To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type ...(WT) K-RAS colorectal cancer (CRC).
Methods
Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m
2
of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal.
Results
Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (
p
= 0.0032).
Conclusion
This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.
Gene profiling using a customized NanoString platform can be applied to routine mycosis fungoides (MF) samples, revealing their specific molecular features. This study shows that MF samples carry a ...signature derived from individual molecular features found in consecutive biopsies.
Abnormal serum potassium levels (K+) in patients with heart failure (HF) relate to worse prognosis. We evaluated whether admission K+ levels predict 1-year outcomes in elderly patients admitted for ...acute HF.
We evaluated 2865 patients aged >74 years from the RICA Spanish Heart Failure Registry, classified according to admission serum K+ levels: hyperkalemia (>5.5 mmol/L), normokalemia (3.5–5.5 mmol/L) and hypokalemia (<3.5 mmol/L). We explored whether K+ levels were significantly associated with one-year all-cause mortality or hospital readmission and their combination.
Mean admission K+ value was 4.3 ± 0.6 mmol/L; 97 patients (3.38%) presented with hyperkalemia and 174 (6.06%) with hypokalemia. Overall, 43% of the patients died or were readmitted for HF during the follow-up period; the risk was higher for those with hyperkalemia (59% vs 41% in hypokalemic patients). The HR for one-year mortality was 1.43 (p = .073) and 1.67 for readmissions (p = .007) when K+ was >5.5 mmol/L and 1.08 (p = .618) and 0.90 (p = .533) respectively for K+ < 3.5 mmol/L. The HR for the combined outcome was 1.59 (1.19–2.13); p = .002 in hyperkalemic patients and 0.96 (0.75–1.23); p = .751in hypokalemic patients. Multivariate analysis showed a significant association of admission K+ values >5.5 mmol/L with the combined outcome of mortality and readmission (HR 1.15 95% CI 1.04–1.27, p = .008).
In patients hospitalized for decompensated HF, admission hyperkalemia predicts a higher mid-term risk for HF readmission and mortality, probably related to the significant higher risk of readmission.
•Abnormal serum potassium (K+) values may be associated with poor health results in heart failure (HF) patients.•At admission, 3.38% of patients presented with hyperkalemia and 6.06% with hypokalemia.•Hyperkalemia at admission predicts a higher one-year-term risk for HF readmission and mortality.•Probably this association is related to the significant higher risk of readmission.
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