OBJECTIVETo evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).

METHODSData of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy.

RESULTSThe median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001).

CONCLUSIONThe mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients.

METHODSA total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed.

RESULTSThe objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients.

CONCLUSIONSBoth CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; administration & dosage ; adverse effects ; Capsules ; Dihydrouracil Dehydrogenase (NADP) ; metabolism ; Disease Progression ; Humans ; Neoplasm Proteins ; metabolism ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pyridines ; administration & dosage ; adverse effects ; Stomach Neoplasms ; drug therapy ; metabolism ; mortality ; pathology ; Tegafur ; administration & dosage ; adverse effects ; Thymidine Phosphorylase ; metabolism

OBJECTIVETo explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients.

METHODSOne hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups.

RESULTSThe baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ=0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ=5.382, P=0.020; 58.4% vs. 34.4%, χ=6.636, P=0.010).

CONCLUSIONRegional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Celiac Artery ; Chemotherapy, Cancer, Regional Perfusion ; adverse effects ; methods ; mortality ; Cisplatin ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Fluorine ; administration & dosage ; adverse effects ; therapeutic use ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Gastrectomy ; Humans ; Leucovorin ; therapeutic use ; Lymph Node Excision ; Neoplasm Recurrence, Local ; prevention & control ; Organoplatinum Compounds ; therapeutic use ; Postoperative Complications ; Recovery of Function ; Stomach Neoplasms ; drug therapy ; mortality ; surgery ; Survival Rate

OBJECTIVETo explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer(MPC).

METHODSBetween April 2014 and October 2015, 35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of 5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary end point was progression free survival. The second end points were overall survival, objective response rate, adverse effects, surgical resection rate for LAPC.

RESULTSAmong 35 patients, 6 patients (17.1%) who dropped out and received less than 2 cycles were excluded for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4 adverse effects. No patients ceased treatment due to adverse effects. The 29 patients received 5 (2-13) cycles were evaluated by efficacy and found partial remission in 16 cases, stable disease in 10 cases, progression disease in 3 cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery after neoadjuvant treatment without perioperative complication and death, and 6 patients accepted R0 resection.

CONCLUSIONSThe mFOLFIRINOX regimen used in the study is well-tolerated in Chinese population with high treatment efficacy on patients with LAPC and MPC. Further investigation of efficacy and adverse effects on more advanced pancreatic cancer patients is necessary.

Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; administration & dosage ; analogs & derivatives ; Disease Progression ; Disease-Free Survival ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Neoadjuvant Therapy ; Organoplatinum Compounds ; administration & dosage ; Pancreatic Neoplasms ; drug therapy ; Tertiary Care Centers ; Treatment Outcome

OBJECTIVE: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. METHODS: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. RESULTS: In total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). CONCLUSION: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration & dosage ; Carcinoma, Squamous Cell/*drug therapy/mortality ; Cisplatin/administration & dosage/*analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Organoplatinum Compounds/administration & dosage ; Retreatment ; Retrospective Studies ; Treatment Outcome ; Uterine Cervical Neoplasms/*drug therapy/mortality

Gastric cancer frequently disseminates to the liver, lung, and bone via hematogeneous, lymphatic, or peritoneal routes. However, gastric adenocarcinoma that metastasize to the colon and that shows typical linea platisca pattern on colonofiberscopy has rarely been reported. Recently, the authors experience a case of advanced gastric cancer with colonic metastases in a 55-year-old female patient. Multiple colonic lymphoid hyperplasias were detected on colonofiberscopy and biopsy revealed metastatic gastric cancer to the colonic wall. She was treated with mFOLFOX (5-FU, oxaliplatin, leucovorin) and has achieved stable disease status without disease progression. Herein, we report a rare case of signet ring-cell gastric cancer which metastasized to the colon in the form of multiple colonic lymphoid hyperplasias.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Colonic Neoplasms/*diagnosis/secondary ; Colonoscopy ; Female ; Fluorouracil/administration & dosage ; Gastroscopy ; Humans ; Hyperplasia/diagnosis ; Leucovorin/administration & dosage ; Middle Aged ; Organoplatinum Compounds/administration & dosage ; Positron-Emission Tomography ; Stomach Neoplasms/*diagnosis/drug therapy ; Tomography, X-Ray Computed

Primary colorectal choriocarcinoma is a rare neoplasm. Only 19 cases have been reported worldwide, most of which involved adenocarcinomas. The prognosis is usually poor, and the standard therapy for this tumor has not been established. A 61-year-old woman presented with constipation and lower abdominal discomfort. She was diagnosed with primary adenocarcinoma with focal choriocarcinomatous differentiation in the sigmoid colon and liver metastasis. Because the serum beta-human chorionic gonadotropin level was not significantly elevated, and because only focal choriocarcinomatous differentiation was diagnosed, we selected the chemotherapy regimen that is used for the treatment of metastatic colorectal adenocarcinoma. The patient survived for 13 months after the initial diagnosis. This is the first case in Korea to assess the suppressive effects of the standard chemotherapy for colorectal adenocarcinoma against coexisting colorectal choriocarcinoma and adenocarcinoma.
Adenocarcinoma/*diagnosis/drug therapy/pathology ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CA-19-9 Antigen/analysis ; Chorionic Gonadotropin, beta Subunit, Human/blood ; Colon, Sigmoid/pathology ; Colonic Neoplasms/*diagnosis/drug therapy/pathology ; Colonoscopy ; Constipation/etiology ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/secondary ; Middle Aged ; Organoplatinum Compounds/therapeutic use ; Prognosis ; Tomography, X-Ray Computed

OBJECTIVETo analyze the characteristics of recurrence in gastric cancer patients after radical gastrectomy and adjuvant chemotherapy.

METHODSThe clinicopathological data of 110 gastric cancer patients who developed recurrence or second primary malignancies after radical gastrectomy and adjuvant chemotherapy with FOLFOX4 regimen or docetaxel plus FOLFOX4 regimen were analyzed retrospectively.

RESULTSThe median time to recurrence was 13.9 months (range, 1.7 to 63.1 months), and the median overall survival was 27.4 months (range, 6.9 to 90.7 months) in the whole group. The median survival time after recurrence was 10.1 months (range, 0.3 to 73.9 months). 82 (74.5%) patients had recurrence within 2 years after gastrectomy. The modes of surgical procedure and lymph node dissection influenced significantly on the time to recurrence (P<0.05 for both). Among the 110 patients with recurrence, 46 (41.8%) patients had peritoneal metastases, 33 (30.0%) had hematogenous metastases and 32 (29.1%) had locoregional lymph node metastases. Single, double, triple and quatro recurrences were observed at the first time of relapse in 78 (70.9%), 21(19.1%), 9(8.2%) and 2 cases (1.8%), respectively. Patients who developed simultaneous quatro recurrence had the poorest prognosis with a median overall survival of 15.2 months, significantly shorter than that of patients with single recurrence (31.8 months, P=0.003). Patients with peritoneal recurrence died most quickly ( mean 5.6 months), and patients with surgical field recurrence alone survived longest (mean 17.1 months).

CONCLUSIONSPeritoneal, hematogenous and locoregional lymph node metastases are the most frequent recurrences after radical gastrectomy and adjuvant chemotherapy in patients with gastric cancer. Single recurrence occurred in most patients at the first relapse. Combination with other adjuvant treatments should be considered besides adjuvant chemotherapy in gastric cancer patients after radical gastrectomy.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Chemotherapy, Adjuvant ; Fluorouracil ; administration & dosage ; Gastrectomy ; methods ; Humans ; Leucovorin ; administration & dosage ; Lymph Node Excision ; Lymphatic Metastasis ; Neoplasm Recurrence, Local ; mortality ; Neoplasms, Second Primary ; Organoplatinum Compounds ; administration & dosage ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; mortality ; therapy ; Taxoids ; administration & dosage ; Time Factors

OBJECTIVETo evaluate the safety and efficacy of gemcitabine combined with S-1 in the treatment of advanced pancreatic cancer.

METHODSA retrospective analysis of the clinical data of 49 patients with advanced pancreatic cancer, who did not receive radiotherapy and chemotherapy, were divided into two groups: the study group (25 cases), and control group (24 cases). Patients in the study group received gemcitabine 1 000 mg/m² via intravenous drip at the first and 8th days, and received S-1 80 mg/m², morning and evening (twice a day) for the first 14 days, and 21 days as a treatment cycle of chemotherapy.The control group was given GEMOX regimen: Gemcitabine 1 000 mg/m² via intravenous drip at the first and 8 days, and oxaliplatin 130 mg/m² via intravenous drip at the first day, and 21 d for a treatment cycle of chemotherapy. The efficacy and adverse reactions in patients of the study and control groups were observed and compared.

RESULTSThe efficiency of the study group was 32.0% and disease control rate was 72.0%. The efficiency of the control group was 25.0% and disease control rate was 58.3%. The differences between the two groups were statistically not significant (P > 0.05 for all). The clinical benefit rate in the study group and control group were 80.0% and 50.0%, respectively, showing a significant difference (P < 0.05). The median survival time was 9.7 months in patients of the study group and 9.0 months in the control group, with a significant difference (P < 0.05). The drug toxicity was well tolerated in both groups, and no chemotherapy-related death occurred. The major adverse reactions were myelosuppression and digestive tract reactions, and the adverse reactions in the study group were lower than those in the control group.

CONCLUSIONSGemcitabine combined with S-1 is effective and safe in the treatment of advanced pancreatic cancer, with less side effects, and can be tolerated by the patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Administration Schedule ; Drug Combinations ; Humans ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pancreatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies ; Tegafur ; administration & dosage ; adverse effects

BACKGROUND/AIMS: The incidence of colorectal cancer has been increasing every year in Korea. Irinotecan- or oxaliplatin-based regimens including biologic agents are known to be effective in patients with advanced colorectal cancer. But in practice, FOLFOX (combination of oxaliplatin, 5-fluorouracil, and leucovorin) or FOLFIRI (combination of irinotecan, 5-fluorouracil, and leucovorin) regimens without biologic agents are more commonly used in Korea due to of the high costs of biologic agents. The aim of this study was to evaluate the efficacy and toxicity of FOLFIRI following FOLFOX4 in patients with advanced colorectal cancer. METHODS: A total of 54 patients with advanced colorectal cancer who were treated between May 2005 and May 2013 with FOLFOX4 as first-line chemotherapy and with FOLFIRI as second-line chemotherapy at Kosin University Gospel Hospital (Busan, Korea) were reviewed retrospectively. RESULTS: A total of 54 patients received second-line FOLFIRI chemotherapy. Five patients (9.3%) had a partial response, 29 patients (53.7%) had a stable disease. The median overall survival was 8.90 months and the median time to progression was 4.33 months. Toxicities were tolerable. CONCLUSIONS: In a Korean population, FOLFIRI as second-line chemotherapy is effective and well tolerated in patients with advanced colorectal cancer after failure of FOLFOX4. Although the efficacy of FOLFIRI in this study was lower than that of second-line FOLFIRI with biologic agents, these results can help in the formulation of a treatment strategy for financially troubled patients.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/administration & dosage/*analogs & derivatives/therapeutic use ; Colorectal Neoplasms/*drug therapy/mortality ; Drug Administration Schedule ; Female ; Fluorouracil/administration & dosage/therapeutic use ; Humans ; Injections, Intravenous ; Leucovorin/administration & dosage/therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds/administration & dosage/therapeutic use ; Republic of Korea ; Retrospective Studies ; Survival Analysis