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Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis.

ABSTRACT: There is a debate whether triplet or doublet chemotherapy should be used as a first-line treatment in patients with advanced or metastatic esophagogastric cancer. Therefore, here we will review the available literature to assess the efficacy and safety of triplet versus doublet chemotherapy as a first-line treatment in patients with advanced esophagogastric cancer. We searched MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) between 1980 and March 2015 for randomized controlled phase II and III trials comparing triplet with doublet chemotherapy and abstracts of major oncology meetings from 1990 to 2014. Twenty-one studies with a total of 3475 participants were included in the meta-analysis for overall survival. An improvement in overall survival (OS) (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.83-0.97) and progression-free survival (PFS) (HR 0.80, 95% CI 0.69-0.93) was observed in favor of triplet. In addition, the use of triplet was associated with better objective response rate (ORR) (risk ratio 1.25, 95% CI 1.09-1.44) compared to doublet. The risks of grade 3-4 thrombocytopenia (6.2 vs 3.8%), infection (10.2 vs 6.4%), and mucositis (9.7 vs 4.7%) were statistically significantly increased with triplet compared to doublet. This review shows that first-line triplet therapy is superior to doublet therapy in patients with advanced esophagogastric cancer. However, the survival benefit is limited and the risks of grade 3-4 thrombocytopenia, infection, and mucositis are increased.

SUBMITTER: Mohammad NH

PROVIDER: S-EPMC4573655 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis.

Mohammad N Haj NH ter Veer E E Ngai L L Mali R R van Oijen M G H MG van Laarhoven H W M HW

Cancer metastasis reviews 20150901 3

There is a debate whether triplet or doublet chemotherapy should be used as a first-line treatment in patients with advanced or metastatic esophagogastric cancer. Therefore, here we will review the available literature to assess the efficacy and safety of triplet versus doublet chemotherapy as a first-line treatment in patients with advanced esophagogastric cancer. We searched MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) between 1980 and March 2015 for randomized ...[more]

PMID: 26267802

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Project description:BACKGROUND:Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first-line chemotherapy in metastatic esophagogastric cancer. MATERIALS AND METHODS:Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14?days and regorafenib 160 mg daily on days 4 to 10 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. RESULTS:Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single-center phase II study (NCT01913639). The most common grade 3-4 treatment-related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6-month PFS was 53% (95% confidence interval [CI], 38%-71%), the objective response rate was 54% (95% CI, 37%-70%), and the disease control rate was 77% (95% CI, 67%-94%). Next-generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum-based chemotherapy. CONCLUSION:Regorafenib (one week on-one week off schedule) is well tolerated in combination with first-line FOLFOX but does not improve 6-month PFS relative to historical control. IMPLICATIONS FOR PRACTICE:Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first-line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD-1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible.

Project description:BackgroundDoublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown.MethodsIn this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint.ResultsOverall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167-208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405-559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142-238; hazard ratio for progression: 1.21, 95 % CI, 0.29-5.02; p = 0.27), while the median OS was 428 (95 % CI, 324-940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193-277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41-7.27; p = 0.69, while the median OS was 273 (95 % CI, 241-459) days (hazard ratio for death: 2.95; 95 % CI, 0.4-21.7; p = 0.51). Grade 3-4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients.ConclusionMoving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

Project description:PURPOSE:To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). METHODS:We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766. RESULTS:The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63-0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88-0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98-1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H. CONCLUSIONS:Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.

Project description:BackgroundSurgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC.Patients and methodsPatients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy.ResultsFifty-three patients were enrolled. The median age was 52 years (range 23-74), 29 (55%) were males, ECOG PS 0-1 was 13 (66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22 (42%) had a single metastatic site, and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1-20] and the median OS was 28.2 months (95% CI 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6-not reached) compared to 9.6 months (95% CI 7.0-18.3) for the non-surgical group, log-rank p = 0.0165. The median OS for both groups was not reached (95% CI 53.3-not reached) and 23.2 months (95% CI 17.0-28.4) respectively, log-rank p = 0.0006. Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively.ConclusionsPatients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible.Trial registrationClinicaltrials.gov , NCT01311050 , registered March 6, 2011, retrospectively registered.

Dataset Information

Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis.

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Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis.

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