Toxicity of chemotherapy regimens in advanced and metastatic pancreatic cancer therapy: A network meta‐analysis

Abstract

This network meta-analysis is adopted in order to compare the toxicity of different chemotherapy regimens in the treatment of advanced/metastatic pancreatic cancer (PC). Randomized controlled trials (RCTs) about different chemotherapy regimens for advanced/metastatic PC were included in this network meta-analysis using Cochrane Library and PubMed electronic databases. The network meta-analysis was performed to combine direct and indirect evidence in order to calculate the odd ratios (OR) and draw a surface under the cumulative ranking (SUCRA) curve. A total of 19 RCTs were enrolled in this network meta-analysis including 12 chemotherapy regimens (Gemcitabine, Gemcitabine + S-1 [tegafur], Gemcitabine + nab-paclitaxel, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, FOLFIRINOX [oxaliplatin + irinotecan + fluorouracil + leucovorin], Gemcitabine + oxaliplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, Gemcitabine + pemetrexed, Gemcitabine + 5-FU, S-1). The incidence of anemia of Gemcitabine + Capecitabine regimen was higher compared with Gemcitabine regimen, Gemcitabine + pemetrexed regimen exhibited the highest incidence rates of anemia and neutropenia; while Gemcitabine + S-1, Gemcitabine + Cisplatin and FOLFIRINOX regimens exhibited the highest incidence rates of neutropenia. However, S-1 regimen exhibited lower incidence rates of leukopenia and thrombocytopenia. Moreover, the incidence rates of nausea/vomiting and rash of Gemcitabine + S-1 regimen were higher compared with Gemcitabine regimen, while Gemcitabine + Cisplatin regimen had the highest incidence rate of nausea/vomiting. This study demonstrated that the hematologic toxicity of S-1 regimen was the lowest, while Gemcitabine regimen exhibited the lowest incidence rate of non-hematologic toxicity, providing guidance for the treatment of advanced/metastatic PC.

Retrospective analysis of efficacy and safety of Gemcitabine-based chemotherapy in patients with metastatic pancreatic adenocarcinoma experiencing disease progression on FOLFIRINOX

“…Also, the longest median OS attained so far in MPA (18 months) was seen in an observational study in which patients were treated sequentially with FOLFIRINOX and Gemcitabine plus Nab-Paclitaxel (8). These data, along with the increased activity of Gemcitabine plus Nab-Paclitaxel shown in the first-line setting (30), set this combination as a valuable option for those progressing on FOLFIRINOX.…”

The Use of (Network) Meta-Analysis in Clinical Oncology

“…The downside of this approach is that only the relative ranks are shown, but the absolute differences between the treatments are not (91). In example, this was the case in multiple NMAs on systemic therapy for advanced pancreatic cancer (82, 84, 85). In contrast, the relative ranking of the treatments can also be evaluated by simply categorizing the effect-sizes between all treatments and an important comparator from high to low, except that the absolute effect are still shown to the readers of the article.…”

“…This can lead to limited network connectivity in NMA and therefore low statistical power (6, 74, 81). There are many examples of published NMAs with low network connectivity and large confidence intervals of the effect-sizes, making it difficult to interpret the results (82–85). For example, in a NMA on first-line palliative systemic treatments of advanced pancreatic cancer, all treatments in the network, for example gemcitabine plus nab-paclitaxel, were connected with only gemcitabine monotherapy (84).…”

Folfirinox versus gemcitabine-cisplatin combination as first-line therapy in treatment of pancreaticobiliary cancer

“…Gemcitabine + Pemetrexed regimens had a relatively higher incidence of toxicity than other regimens [19]. Another meta-analysis comparing toxicity profiles of these regimen, Gemcitabine + Cisplatin and FOLFIRINOX regimens exhibited the highest incidence rates of neutropenia [20].…”