No abstract available.
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/*analogs & derivatives/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Male ; Organoplatinum Compounds/therapeutic use ; Stomach Neoplasms/*drug therapy

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

Pancreatic cancer is a very lethal cancer. It is the 5th most common cause for cancer related mortality in Korea. Most of patients have unresectable pancreatic cancer, and systemic chemotherapy remains the only treatment option for them. Gemcitabine has been adopted as the standard first-line agent for advanced pancreatic cancer, but the progression free survival with gemcitabine is short. Many of patients need further treatment. We reviewed the clinical trials of second line chemotherapy for gemcitabine refractory pancreatic cancer and tried to show currently available treatment options.
Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Camptothecin/therapeutic use ; Deoxycytidine/analogs & derivatives/therapeutic use ; Drug Therapy, Combination ; Fluorouracil/therapeutic use ; Humans ; Organoplatinum Compounds/therapeutic use ; Pancreatic Neoplasms/*drug therapy ; Taxoids/therapeutic use

Colorectal cancer is the second most common malignant tumor in China. The FOLFOXIRI regimen, which combines 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan, is a high-intensity and highly effective chemotherapy regimen. However, the original regimen is poorly tolerated in Chinese patients. In order to promote the standardized and rational application of FOLFOXIRI regimen by clinicians in China, "
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Camptothecin/therapeutic use* ; China ; Colorectal Neoplasms/drug therapy* ; Consensus ; Fluorouracil/therapeutic use* ; Humans ; Irinotecan/therapeutic use* ; Leucovorin/therapeutic use* ; Organoplatinum Compounds/therapeutic use* ; Oxaliplatin ; Treatment Outcome

OBJECTIVEThe patients with recurrent or refractory neuroblastoma have a very poor prognosis and high mortality. 10-hydroxycamptothecin (HCPT) is a new agent extracted from comptotheca acuminate, a native plant. It has been shown to be very effective in some solid tumors such as gastric and colon cancers, lung cancers and ovary cancers. However, its efficacy in neuroblastoma has not been determined. This study aimed to investigate the therapeutic effects of HCPT in the treatment of recurrent or refractory neuroblastoma in children.

METHODSTen children with recurrent neuroblastoma and two children with refractory neuroblastoma were treated with HCPT. Of them, 5 children with recurrent neuroblastoma were treated with HCPT alone, and the other 7 patients received combination chemotherapy of HCPT plus other agents. The HCPT alone treatment group was injected with HCPT (7.5 mg/m2 daily) for 14 consecutive days. The combination chemotherapy group was alternately treated with the modified new protocol A1 (cyclophosomide 1 200 mg/m2 on day 1, etoposide 100 mg/m2 on days 1-5, HCPT 5 mg/m2 on days 1-3, cisplatin 90 mg/m2 on day 4) and the modified protocol B (ifosfomide 1.5 g/m2 on days 1-5, HCPT 5 mg/m2 on days 1-3, carboplatin 450 mg/m2 on day 2).

RESULTSFour patients (33.3%) achieved partial remission and 8 patients (66.7%) had stable disease. The median remission duration was 3.5 months (2-5 months). HCPT treatment as a single agent resulted in mild side effects. Myelosuppression and digestive disorders were found as the main adverse events in the combined chemotherapy group. No chemotherapy related deaths were found.

CONCLUSIONSHCPT is safe and effective in the treatment of recurrent or refractory neuroblastoma. The toxicities of HCPT are tolerable. The long-term efficacy of HCPT warrants further research.

Adolescent ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Camptothecin ; analogs & derivatives ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Male ; Neuroblastoma ; drug therapy ; Recurrence

BACKGROUNDTo compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer.

METHODSLiterature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010. Two authors drew the details of trial design, characteristics of patients, outcomes, and toxicity from the studies included. Data analysis was performed by RevMan 4.2.

RESULTSAccording to the screening criteria, 7 clinical studies with 2095 participants of advanced colorectal cancer were included in this meta analysis. The baseline characteristics of irinotecan group were similar to those of oxaliplatin group. The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR) = 0.82, 95% confidence interval (95%CI) (0.70, 0.96), P = 0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P = 0.008). In the comparison of grade 3 - 4 toxicity between the two groups, the incidences of nausea, emesis, diarrhoea and alopecia in irinotecan group were higher than those in oxaliplatin group (RR = 1.94, 95%CI (1.22, 3.09), P = 0.005; 1.71, 95%CI (1.34, 2.18), P < 0.001; 14.56, 95%CI (4.11, 51.66), P < 0.0001), respectively. However, the incidence of neurotoxicity, neutropenia and thrombocytopenia in irinotecan group were lower than those in oxaliplatin group (RR = 0.06, 95%CI (0.03, 0.14), P < 0.00001; 0.70, 95%CI (0.55, 0.91), P = 0.006; 0.18, 95%CI (0.05, 0.61), P = 0.006), respectively.

CONCLUSIONSBoth irinotecan and oxaliplatin combined with 5-fluorouracil and leucovorin were effective in the first-line therapy of advanced colorectal cancer. However, the combined regimen of oxaliplatin plus 5-fluorouracil and leucovorin is more excellent. Irinotecan tended to result in more gastrointestinal tract reactions than oxaliplatin did, but the myelosuppression and neurotoxicity were more frequent in oxaliplatin regimen than irinotecan regimen.

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Organoplatinum Compounds ; therapeutic use ; Treatment Outcome

Preoperative concurrent chemoradiotherapy based on 5-fluorouracil (5-FU) is an standard treatment mode for patients with locally advanced rectal cancer (LARC). Currently, more and more interests has now focused on new chemotherapeutic drugs, such as capecitabine, oxaliplatin, irinotecan, bevacizumab, and cetuximab in this treatment mode. Many prospective phase I-III clinical trials have been developed to explore these new drugs efficacy in the neoadjuvant chemoradiation (nCRT) for patients with LARC. Some results are very encouraging, yet others are undesirable. Capecitabine has been widely recognized in the nCRT for patients with LARC, and has the tendency to replace 5-FU. However, there are some controversies for oxaliplatin, irinotecan, and biologically targeted drugs in the nCRT mode because of their limited clinical benefits. It is potentially the development direction to study the mutual interaction mechanism among concurrent drugs or radiation and biologically targeted drugs, find new predicatively responsive targets, and screen the appropriate patient in the treatment of neoCRT for patients with LARC in the future.
Antineoplastic Agents ; therapeutic use ; Camptothecin ; analogs & derivatives ; therapeutic use ; Capecitabine ; Chemotherapy, Adjuvant ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Humans ; Organoplatinum Compounds ; therapeutic use ; Rectal Neoplasms ; drug therapy ; surgery

Antineoplastic Agents, Phytogenic ; therapeutic use ; Camptothecin ; analogs & derivatives ; therapeutic use ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Rectal Neoplasms ; drug therapy ; pathology ; Remission Induction

BACKGROUNDStudies have shown that irinotecan can improve survival in patients with advanced or recurrent gastric cancer, but the overall benefit of irinotecan in the treatment of advanced or recurrent gastric cancer remains controversial. The aim of this study was to evaluate the benefits and risks of irinotecan for survival in patients with advanced or recurrent gastric cancer. Method We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major conferences for relevant clinical trials. We included randomized controlled trials that reported on the efficacy and safety of irinotecan in patients with advanced or recurrent gastric cancer. Outcomes were analyzed by survival rate, objective response rate (ORR), and toxicity. Furthermore, the analysis was further stratified by factors that could affect the treatment effects.

RESULTSEight trials recruiting 1 546 patients with advanced or recurrent gastric cancer were included in the analysis. Overall, irinotecan therapy was associated with a 6% improvement in survival rate, but this difference was not statistically significant (odds ratio (OR) 0.94; 95% confidence interval (95% CI) 0.70-1.27; P = 0.69). However, irinotecan therapy had more frequent ORR than irinotecan-free arm (OR 1.70; 95% CI 1.34-2.17; P < 0.001). Furthermore, irinotecan therapy was associated with a clinically and statistically significant increase in the risk for declined hemoglobin, hyponatremia, and diarrhea, but it also protected against thrombocytopenia risk when compared with irinotecan-free therapy.

CONCLUSIONSThere is no evidence to support the use of irinotecan therapy in patients with advanced or recurrent gastric cancer; however, given the significant advantage in ORR irinotecan therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.

Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; analogs & derivatives ; therapeutic use ; Humans ; Neoplasm Recurrence, Local ; drug therapy ; Stomach Neoplasms ; drug therapy ; Treatment Outcome

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Camptothecin/therapeutic use* ; Case-Control Studies ; Colorectal Neoplasms/drug therapy* ; Fluorouracil/therapeutic use* ; Humans ; Leucovorin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Prognosis ; Retrospective Studies