Capecitabine Plus Oxaliplatin and Bevacizumab, Followed by Maintenance Treatment With Capecitabine and Bevacizumab for Patients Aged &gt; 75 Years With Metastatic Colorectal Cancer

Petrioli, Roberto; Francini, Edoardo; Cherri, Sara; Torre, Pamela; Fiaschi, Anna Ida; Miano, Salvatora Tindara; Marrelli, Daniele; Rovello, F; Francini, Guido

doi:10.1016/j.clcc.2018.07.002

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…In contrast, few studies showed that treatment with chemotherapy was signi cantly effective in prolonging OS in super-elderly patients. In a previous study of chemotherapy under the age of 75, the most frequent adverse event ≥ grade 3 was neutropenia, with grade 3 neutropenia reported in 11.1% of patients; meanwhile, grade 3 fatigue was only reported in 2.8% of patients [8]. In our study, most patients in the super-elderly group (n = 10, 83%) received combination chemotherapy, the most common of which was an oxaliplatin-based regimen.…”

Section: Discussionsupporting

confidence: 48%

“…The study included 36 patients (13 patients aged ≥ 80 years), and 21 patients (58.3%) received second-line chemotherapy. The median PFS and OS was 8.8 months (95% CI: 6.7-10.3 months) and 20.8 months (95% CI: 16.1-26.4 months), respectively [8].…”

Section: Discussionmentioning

confidence: 96%

“…Several studies have attempted to evaluate chemotherapy in elderly patients. However, most of them have included elderly patients aged ≥ 65 years with mCRC, and others have included patients aged ≥ 70 years or patients of different ages [7][8][9]. Moreover, super-elderly patients (aged ≥ 80 years) have worse performance status (PS) and more comorbidities than younger patients.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Therapeutic Features and Prognostic Factors of Metastatic Colorectal Cancer Over Age 80: A Retrospective Study

Hisada

Takahashi

Kubota

et al. 2020

Preprint

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Background Colorectal cancer (CRC) is one of the most common cancers in the world. The number of elderly patients with CRC increases due to aging of the population. There are few studies that examined chemotherapy and prognostic factors in metastatic colorectal cancer (mCRC) patients aged ≥80 years. We assessed the efficacy of chemotherapy and prognostic factors among patients with mCRC aged ≥80 years.Methods We retrospectively analyzed clinical and laboratory findings of 987 patients newly diagnosed with CRC at Asahi General Hospital (Chiba, Japan) between January 2012 and December 2016. Kaplan-Meir method was used for the overall survival (OS) and the log-rank test was used to identify difference between patients. A multivariate Cox proportional hazard regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs) of prognostic factors among super-elderly patients.Results In total, 260 patients were diagnosed with mCRC (super-elderly group: n = 43, aged ≥80 years and younger group, n = 217, aged <80 years). The performance status and nutritional status were worse in the super-elderly group than in the younger group. The OS of super-elderly patients who received chemotherapy was worse than that of younger patients (18.5 vs. 28.8 months; P = 0.057), although the difference was not significant. The OS of patients who received chemotherapy tended to be longer than that of those who did not; however, there were no significant differences in OS in the super-elderly group (18.5 vs. 8.4 months P = 0.33). Multivariate analysis revealed that carcinoembryonic antigen levels ≥5 ng/mL (hazard ratio: 2.27; 95% CI: 1.09–4.74; P = 0.03) and prognostic nutritional index ≤35 (hazard ratio: 8.57; 95% CI: 2.63–27.9; P = 0.0003) were independently associated with poor OS in the super-elderly group.Conclusions Patients with mCRC aged ≥80 years had lower OS than younger patients even though they received chemotherapy. Carcinoembryonic antigen and prognostic nutritional index were independent prognostic factors in super-elderly patients with mCRC, but chemotherapy was not.Trial registration retrospectively registered.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Clinical and Therapeutic Features and Prognostic Factors of Metastatic Colorectal Cancer Over Age 80: A Retrospective Study

Hisada

Takahashi

Kubota

et al. 2020

Preprint

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“…Currently, drug combination therapies have become increasingly popular to reduce drug side effects and overcome chemoresistance 6. Combination of oxaliplatin with conventional chemotherapy drugs such as capecitabine has improved the survival of colon cancer patients 7. Alantolactone is a sesquiterpene lactone isolated from the roots of Inula helenium L , a traditional chinese herbal medicine which has been shown to possess strong anti-inflammatory and antitumor activities 8,9.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of oxaliplatin-induced colon cancer cell apoptosis by alantolactone, a natural product inducer of ROS

Cao

Xia

et al. 2019

Int. J. Biol. Sci.

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Colon cancer is a malignant type of cancer with high prevalence and is one of the primary causes of cancer-related deaths. Oxaliplatin plays a significant role in the treatment of cancer, but the application of oxaliplatin is restricted due to its toxic side effects and drug resistance in clinical practice. Therefore, there is an urgent need for new strategies that can synergize with oxaliplatin for confronting colon cancer. Alantolactone (ALT), a natural sesquiterpene lactone, possesses antitumor properties in a number of cancer cell lines. In the present study, we investigated how ALT acts synergistically with oxaliplatin on human colorectal cancer HCT116 and RKO cells in vitro and in vivo . We observed that ALT strengthened the effect of oxaliplatin-induced growth restrain and apoptosis in HCT116 and RKO cells. It is through a mechanism concerning remarkable accumulation of intracellular reactive oxygen species (ROS) and activation of JNK and p38 MAPK signaling pathways. These changes ultimately induced apoptosis of HCT116 and RKO cells. Pretreatment of cells with the ROS reversal agent NAC significantly blocked the apoptosis induced by the combination treatment, and suppressed expression of JNK and p38 phosphorylation in HCT116 and RKO cells. In the xenograft model, the combination therapy displayed stronger antitumor activity compared with single agents. Immunohistochemistry of subsequent treatment tumors showed a significant decrease in proliferation as compared to either of the treatments alone. These results suggest that the combination treatment with ALT and oxaliplatin may become a potential therapeutic strategy for colon cancer.

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“…It can also reduce the risk of recurrence in patients with high-risk colon cancer findings at surgery. 5-Fluorouracil (5-FU) and salinomycin (Sal) are common chemotherapeutic agents used to treat with CRC or recurrence after CRC surgery [4–7]. However, these drugs usually lead to severe side effects, including hand-foot syndrome, neuropathy, and allergic or sensitivity reactions [8,9].…”

Section: Introductionmentioning

confidence: 99%

Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer

Gao

Zhou

Pang

et al. 2019

Free Radical Research

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The thunder god vine (Tripterygium wilfordii Hook. F) is traditionally used for inflammationrelated diseases in traditional Chinese medicine. In recent years, celastrol (a natural compound from the root of the thunder god vine) has attracted great interest for its potential anticancer activities. The free radical nitric oxide (NO) is known to play a critical role in colorectal cancer growth by promoting tumour angiogenesis. However, how celastrol influences the NO pathway and its mechanism against colorectal cancer is largely unknown. In this study, we investigated the effects and mechanism of celastrol on nitric oxide synthase (NOS) and the angiogenesis pathway in colorectal cancer. Our data show that celastrol inhibited HT-29 and HCT116 cell proliferation, migration, and NOS activity in the cytoplasm. The antiproliferation activity of celastrol was associated with the inhibition of iNOS and eNOS in colorectal cancer cells. Treatment with celastrol inhibited colorectal cancer cell growth and migration, and was associated with suppression of the expression of key genes (TYMP, CDH5, THBS2, LEP, MMP9, and TNF) and proteins (IL-1b, MMP-9, PDGF, Serpin E1, and TIMP-4) involved in the angiogenesis pathway. In addition, combinational use of celastrol with 5-fluorouracil, salinomycin, 1400 W, and L-NIO showed enhanced inhibition of colorectal cancer cell proliferation and migration. In sum, our study suggests that celastrol could suppress colorectal cancer cell growth and migration, likely through suppressing NOS activity and inhibiting the angiogenesis pathway.

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Capecitabine Plus Oxaliplatin and Bevacizumab, Followed by Maintenance Treatment With Capecitabine and Bevacizumab for Patients Aged > 75 Years With Metastatic Colorectal Cancer

Abstract: CAPOX/Bev, followed by Cap/Bev as maintenance treatment, is safe and effective in terms of PFS and OS for elderly patients aged > 75 years with mCRC.

Cited by 10 publications

References 30 publications

Clinical and Therapeutic Features and Prognostic Factors of Metastatic Colorectal Cancer Over Age 80: A Retrospective Study

Clinical and Therapeutic Features and Prognostic Factors of Metastatic Colorectal Cancer Over Age 80: A Retrospective Study

Enhancement of oxaliplatin-induced colon cancer cell apoptosis by alantolactone, a natural product inducer of ROS

Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer

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