RÉSUMÉ
OBJECTIVE: To evaluate the safety and efficacy of the granisetron transdermal delivery system (GTDS) combined with Dexamethasone for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving Capecitabine plus Oxaliplatin (CapeOX) therapy. DESIGN: Open-label, prospective, multi-center phase II trial. SETTING: Three institutions. PARTICIPANTS: Fifty-four patients scheduled to receive CapeOX chemotherapy. INTERVENTIONS: Participants received GTDS (3.1 mg applied to the upper arm 48 h before chemotherapy, replaced on day 5, and discarded on day 12) and Dexamethasone. MAIN OUTCOME MEASURES: The primary endpoint was the complete control rate of CINV. Secondary endpoints included the duration of delayed complete control, complete control rate in the acute phase, safety, and quality of life. RESULTS: The complete control rate for delayed CINV over the entire period (25-480 h) was 72.7% (95% CI 0.57-0.88). The duration of delayed complete control was 17.2 ± 4.5 days, with 51.5% of patients experiencing no nausea during the delayed phase. The complete control rate in the acute phase was 81.8% (95% CI 0.69-0.95). No serious adverse events related to the antiemetic regimen were reported. CONCLUSION: Prolonged administration of GTDS is safe and effective for preventing CINV in patients with gastrointestinal malignancies treated with CapeOX. TRIAL REGISTRATION: ClinicalTrials.gov registry (NCT05325190); registered on October 10, 2021.
Sujet(s)
Administration par voie cutanée , Protocoles de polychimiothérapie antinéoplasique , Capécitabine , Granisétron , Nausée , Oxaliplatine , Vomissement , Humains , Mâle , Femelle , Granisétron/administration et posologie , Granisétron/usage thérapeutique , Adulte d'âge moyen , Capécitabine/administration et posologie , Capécitabine/effets indésirables , Oxaliplatine/administration et posologie , Oxaliplatine/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Nausée/induit chimiquement , Nausée/prévention et contrôle , Vomissement/induit chimiquement , Vomissement/prévention et contrôle , Vomissement/traitement médicamenteux , Sujet âgé , Études prospectives , Adulte , Antiémétiques/administration et posologie , Antiémétiques/usage thérapeutique , Qualité de vie , Dexaméthasone/administration et posologie , Dexaméthasone/usage thérapeutiqueRÉSUMÉ
BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.
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Anticorps monoclonaux humanisés , Protocoles de polychimiothérapie antinéoplasique , Jonction oesogastrique , Fluorouracil , Leucovorine , Composés organiques du platine , Récepteur FGFR2 , Tumeurs de l'estomac , Humains , Mâle , Tumeurs de l'estomac/traitement médicamenteux , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/mortalité , Femelle , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Fluorouracil/administration et posologie , Fluorouracil/usage thérapeutique , Leucovorine/usage thérapeutique , Leucovorine/administration et posologie , Adulte d'âge moyen , Anticorps monoclonaux humanisés/usage thérapeutique , Sujet âgé , Jonction oesogastrique/anatomopathologie , Composés organiques du platine/usage thérapeutique , Composés organiques du platine/administration et posologie , Adulte , Méthode en double aveugle , Tumeurs de l'oesophage/traitement médicamenteux , Tumeurs de l'oesophage/anatomopathologie , Extrême-Orient , Sujet âgé de 80 ans ou plus , Taux de survie , Peuples d'Asie de l'EstRÉSUMÉ
BACKGROUND: Non-small cell cancer (NSCLC) patients with concomitant epidermal growth factor receptor (EGFR) and TP53 mutations have a poor prognosis with the treatment of tyrosine kinase inhibitors (TKIs), and may benefit from a combination regimen preferentially. The present study aims to compare the benefits of EGFR-TKIs and its combination with antiangiogenic drugs or chemotherapy in patients with NSCLC harboring EGFR and TP53 co-mutation in a real-life setting. METHODS: This retrospective analysis included 124 patients with advanced NSCLC having concomitant EGFR and TP53 mutations, who underwent next-generation sequencing prior to treatment. Patients were classified into the EGFR-TKI group and combination therapy group. The primary end point of this study was progression-free survival (PFS). The Kaplan-Meier (KM) curve was drawn to analyze PFS, and the differences between the groups were compared using the logarithmic rank test. Univariate and multivariate cox regression analysis was performed on the risk factors associated with survival. RESULTS: The combination group included 72 patients who received the regimen of EGFR-TKIs combined with antiangiogenic drugs or chemotherapy, while the EGFR-TKI monotherapy group included 52 patients treated with TKI only. The median PFS was significantly longer in the combination group than in the EGFR-TKI group (18.0 months; 95% confidence interval [CI]: 12.1-23.9 vs. 7.0 months; 95% CI: 6.1-7.9; p < 0.001) with greater PFS benefit in TP53 exon 4 or 7 mutations subgroup. Subgroup analysis showed a similar trend. The median duration of response was significantly longer in the combination group than in the EGFR-TKI group. Patients with 19 deletions or L858R mutations both achieved a significant PFS benefit with combination therapy versus EGFR-TKI alone. CONCLUSION: Combination therapy had a higher efficacy than EGFR-TKI alone for patients with NSCLC having concomitant EGFR and TP53 mutations. Future prospective clinical trials are needed to determine the role of combination therapy for this patient population.
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Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/génétique , Études rétrospectives , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Association thérapeutique , Récepteurs ErbB/génétique , Inhibiteurs de l'angiogenèse , Protéine p53 suppresseur de tumeur/génétiqueRÉSUMÉ
BACKGROUND: The significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM. PATIENT AND METHODS: The PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed. RESULTS: The main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor. CONCLUSION: Our findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.
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Tumeurs colorectales , Tumeurs du foie , Tumeurs du pancréas , Tumeurs du péritoine , Humains , Tumeurs du péritoine/traitement médicamenteux , Score de propension , Tumeurs colorectales/anatomopathologie , Perfusions artérielles , Tumeurs du pancréas/traitement médicamenteux , Tumeurs du pancréas/anatomopathologie , Tumeurs du foie/secondaire , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Artère hépatique/anatomopathologie , Tumeurs du pancréasRÉSUMÉ
Primary malignant melanoma of the cervix (PMMC) is a rare and aggressive tumor. Studies on clinicopathological findings, treatment outcomes, and prognostic factors of this disease are lacking. We reviewed 14 cases of PMMC recorded from January 1972 to February 2017 at the Tianjin Medical University Cancer Institute and Hospital. Twelve (85.7%) of the 14 patients presented a history of vaginal bleeding and 11 (78.6%) underwent surgery. The overall survival was 3-70 months, with a median time of 13.7 months. Patients who underwent surgery (P=0.035) had high survival rates, whereas those with lymph node metastasis and late International Federation of Gynecology and Obstetrics stage had poor survival rates, but did not show a significant difference (P=0.187 and 0.053, respectively) compared with those without node metastasis and early International Federation of Gynecology and Obstetrics stage. PMMC is a highly aggressive tumor with a poor prognosis. Surgical resection is the main treatment of choice for PMMC.
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Mélanome/diagnostic , Tumeurs du col de l'utérus/diagnostic , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mélanome/mortalité , Mélanome/anatomopathologie , Adulte d'âge moyen , Analyse de survie , Tumeurs du col de l'utérus/mortalité , Tumeurs du col de l'utérus/anatomopathologieRÉSUMÉ
Sophoridine is an alkaloid extracted from Sophora alopecuroides that has extensive pharmacological actions. In the present study, the effect of sophoridine on cell growth of human medulloblastoma and its mechanism were investigated. Human medulloblastoma D283-Med cells were incubated with 0, 0.5, 1 or 2 mg/ml sophoridine for 24, 48 or 72 h. Cell proliferation and cytotoxicity were analyzed using MTT and lactate dehydrogenase assays, respectively. Next, analyses of cell apoptosis and caspase-3/8 activity were performed using flow cytometry or spectrophotometry, respectively. Lastly, the change in FoxM1, TrkB, BDNF, NF-κB and AP-1 expression was investigated using western blot analysis. In the present study, treatment with sophoridine significantly suppressed cell growth and induced apoptosis in human medulloblastoma cells. In addition, sophoridine significantly increased cytotoxicity and caspase-3/8 activity in human medulloblastoma. Finally, it was found that sophoridine suppresses the protein expression of FoxM1, TrkB, BDNF NF-κB and AP-1 in human medulloblastoma cells. The present study suggests that sophoridine suppresses cell growth of human medulloblastoma through the inhibition of the FoxM1, NF-κB and AP-1 signaling pathway.
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OBJECTIVE: To evaluate the efficacy and safety of Chinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion for pancreatic cancer with liver metastases (PCLM). METHODS: We retrospectively selected 292 patients with PCLM who were treated by Chinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion at Tianjin Medical University Cancer Hospital from January 2001 to December 2010. All patients were assigned to the Western medicine treatment group (157 cases) and the integrative medicine treatment group (135 cases). Patients in the Western medicine treatment group were treated with gemcitabine (GEM)-based chemotherapy, and partial of them received regional arterial perfusion. Those in the integrative medicine treatment group additionally took Chinese herbs of clearing heat and eliminating mass for at least 4 weeks. The median survival time (MST) , adverse reactions and the incidence of complications were observed. RESULTS: There was no statistical significance in general data between the two groups (P > 0.05). There was statistical difference in MST between the two groups (4.8 months vs 5.5 months, P < 0.05). No death occurred during chemotherapy or regional arterial perfusion. All toxic or adverse reactions were tolerable. CONCLUSION: Chinese herbal medicine combined with systemic chemotherapy and/or regional arterial perfusion was effective and safe, and it could be optimally selected as palliative therapy for PCLM.
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Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Thérapies complémentaires/méthodes , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/secondaire , Tumeurs du pancréas/traitement médicamenteux , Désoxycytidine/analogues et dérivés , Médicaments issus de plantes chinoises/usage thérapeutique , Humains , Tumeurs du pancréas/anatomopathologie , Études rétrospectives ,RÉSUMÉ
AIM: To investigate the anticancer activity of a chinese medical mixture, WRCP (warming and relieving Cold Phlegm), on hepatocarcinoma Bel-7402 cells. METHODS: Fingerprints of WRCP, which were composed of aqueous extracts of Aconitum carmichaeli, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng and Gekko swinhonis Guenther, and aconitine, which could be isolated from Aconitum carmichaeli and have the potential toxicity, were identified by high pressure liquid chromatography. Bel-7402 cells were grown in the presence of WRCP, As(2)O(3) or all-trans-retinoic acid (ATRA). Cell proliferation and viability were determined by trypan blue stain. Apoptosis and cell cycle of Bel-7402 cells were detected by flow cytometry. Morphologic and ultrastructural variations were determined under optic and electronic microscopy. The secretion of alpha-fetoprotein and albumin was detected by radioimmunoassay. RESULTS: The average quality of aconitine is 1.15 +/- 0.10 microg per 7.5 g extracts. WRCP could suppress the proliferation and viability of Bel-7402 cells. The percentage of apoptosis cells and S phase cells increased on WRCP-treated cells. Treated with WRCP, Bel-7402 cells showed ultrastructural features of differentiation. The alpha-fetoprotein secretion decreased while the albumin secretion increased (P < 0.001, P < 0.001, respectively) markedly in WRCP-treated cells. CONCLUSION: WRCP can affect the proliferation, differentiation and apoptosis of Bel-7402 cells. It can arrest cells in S phase and has strong cytotoxicity to Bel-7402 cells.