5-fluorouracil In Patients Research Articles

Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer.

This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. Preoperative DCF (docetaxel, 70mg/m2/day, day 1; cisplatin, 70mg/m2/day, day 1; fluorouracil, 750mg/m2/day, days 1-5) was repeated every 3weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3'-UTR 0bp/0bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). ABCC2-24C > T (rs717620), TYMS 3'-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

Adjuvant chemotherapy in ypStage III locally advanced rectal cancer after neoadjuvant treatment with an oxaliplatin-based regimen.

e15628 Background: Fluorouracil -based neoadjuvant chemoradiotherapy(CRT) followed by total mesorectal excision and adjuvant chemotherapy is the standard treatment for locally advanced rectal cancer (LARC). Adjvuant FOLFOX improved survival benefit compared with fluorouracil in patients with ypStage II andIII after CRT. However, induction or consolidation chemotherapy with FOLFOX before surgery had been the new standard for LARC. Whether adjuvant chemotherapy with FOLFOX still improves survival outcomes in ypStage III patients previously exposed to oxaliplatin-based treatment was unknwon. Methods: Patients with LARC receiving oxaliplatin-based neoadjuvant treatment from January 2015 to December 2019 were retrospective analyzed. The inclusion criteria included neoadjuvant FOLFOX chemotherapy alone or induction chemotherpay, concurrent FOLFOX and consolidation chemotherapy before CRT. The duration of neoadjuvant oxaliplatin exposure time was less than 4 months. The efficacy of adjvuant FOLFOX chemotherapy was analyzed among these ypStage III patients according to adjuvant chemotherapy cycles after surgery. Results: A total of 227 patients with ypStage III were enrolled, with the 3-year DFS rate of 46.1% (95%Cl 37.3%-54.9%).Among these patients, 193 patients received adjuvant FOLFOX chemotherapy, including 7 patients had ≤ 2 cycles of adjuvant treatment. And 34 patients had observation after surgery. The 3-year DFS rates bewteen FOXFOL adjvuant chemotherapy group and observation group were 44.7% vs. 56.5%, respectively (HR, 1.190, 95%Cl 0.6246-2.267, P = 0.597). Forty-one patients had ≤ 2 cycles of adjuvant treatment. The 3-year DFS was 43.6% vs. 60.4% (P = 0.597) between pateints receiving over 2 cycles of adjvuant chemotherapy and ≤ 2 cycles of treatment. Conclusions: Among ypStage III LARC pateints after neoadjuvant treatment with Oxaliplatin-Based regimen, adjuvant chemotherapy with FOLFOX failed to improved surival benefit. More enhanced regimen might be necessary for these oxalipatin-resistant patients.

Induction chemotherapy with nanosomal docetaxel lipid suspension (NDLS), cisplatin, and fluorouracil in patients with locally advanced head and neck squamous cell carcinoma.

6074 Background: Nanosomal docetaxel lipid suspension (NDLS), a polysorbate-80 and ethanol free formulation, was developed to overcome the toxicity issues and to improve disease outcomes associated with conventional docetaxel. We evaluated the safety and efficacy of NDLS based TPF (NDLS, cisplatin and 5-fluorouracil [FU]) induction chemotherapy in patients with inoperable/unresectable Locally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC). Methods: In this multicentric, single arm, open label, Phase IV clinical study, patients with inoperable/ unresectable LA HNSCC received induction chemotherapy with NDLS (75 mg/m2; Day 1), cisplatin (75 mg/m2; Day 1) and 5-FU (750 mg/m2/day for 5 days) based TPF regimen every 3 weeks (q3w) for 4 cycles followed by radiotherapy. The study outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: Fifty patients were enrolled in this study. Most of the patients belonged to the age group of 35-64 years (86%) and had a WHO performance status of 1 (66%). In the modified intent-to-treat (mITT) population ( n = 40), the ORR after NDLS based TPF induction chemotherapy was 42.5%, which increased to 60.0% after loco-regional therapy. In the per-protocol (PP) population ( n = 14), the ORR was 64.3%, which increased to 80.0% after loco-regional therapy (Table). At 2 years, the PFS and OS rates were 82.5% and 97.5%, respectively, in the mITT population and 85.7% and 100% respectively, in the PP population. The most common grade 3/4 adverse effects reported were neutropenia (10%), leukopenia (6%), febrile neutropenia (4%), asthenia (2%), diarrhea (2%), and thrombocytopenia (2%) respectively. Grade 3/4 infusion-related reactions, hyperglycemia or neuropathy were not reported. Conclusions: NDLS based induction chemotherapy was effective and well-tolerated in the treatment of inoperable LA HNSCC and showed high response rates. Clinical trial information: CTRI/2017/12/010938 .[Table: see text]

One day versus two days of hepatic arterial infusion with oxaliplatin and fluorouracil for patients with unresectable hepatocellular carcinoma

BackgroundHepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil.MethodsThis study included patients with a primary diagnosis of unresectable HCC. These patients received HAIC for 1 day or 2 days. The overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were compared. The propensity score matching (PSM) was used to reduce bias. Peripheral blood samples before the treatments were collected and used to measure the concentration of TYMS through enzyme-linked immunosorbent assay (ELISA). ELISA was performed according to the manufacturers’ guidelines.ResultsWe included 368 patients for this study: 248 in the HAIC 1d group and 120 in the HAIC 2d group. There was no significant difference of OS between the two groups (14.5 for HAIC 1d vs 15.3 months for HAIC 2d, p=0.46). Compared with the HAIC 1d group, the HAIC 2d group did not prolong the PFS (7.3 vs 7.5 months, p=0.91) or elevate the tumor response (42.5% vs 39.1%, p=0.53) per RECIST 1.1. In the PSM cohort, the efficacy between the two groups was similar. The total frequencies of grade 3–4 events were higher with the HAIC 2d group than with the HAIC 1d group, especially in the PSM cohort (p=0.043). Additionally, patients with TYMS low level might benefit longer OS from the HAIC 2d group (18.7 vs 13.6 months, p=0.014).ConclusionsThere was not much of a difference in efficacy between the two groups, but the HAIC for 1 day might be safer, which needed further research. The level of TYMS might be the predictive biomarkers.

Assessment of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil in patients with oral cavity cancer.

Chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been studied in patients with head and neck cancer. Its impact on patients with oral cavity cancer was not specified. We consecutively reviewed medical files of patients with untreated oral cavity cancer who received neoadjuvant TPF chemotherapy in our department from January 2017 to April 2020. Outcomes included the objective response to TPF chemotherapy, factors associated with the response, and progression and survival in different response groups. A total of 167 patients were included, with half of stage IV disease. Complete or partial response was observed in 51 patients. A total of 91 patients had stable disease, and 25 patients had progressive disease. The response was not associated with age, sex, anatomic subsite, and the tumor's T stage. It was related with N stage (p < 0.001) and clinical stage (p=0.004). Most patients with bulky nodes or nodes with obvious necrosis showed low response or even progressed after neoadjuvant TPF chemotherapy. The planned surgery was conducted in 159 patients. Disease relapse mostly occurred in 2 years after treatment. The 2-year overall survival and the progression-free survival were 89.0% and 85.2% for patients with complete or partial response, 62.4% and 55.6% for patients with stable disease, and 12.5% and 4.2% for patients with progressive disease, respectively. The response of neoadjuvant TPF chemotherapy in patients with oral cavity cancer is related to disease stage, especially the nodal stage. Patients with complete or partial response developed less progression events and better survival.

Olaparib ± bevacizumab versus bevacizumab + fluorouracil in patients with unresectable or metastatic colorectal cancer not progressing on first-line FOLFOX + bevacizumab: Phase III LYNK-003 study.

TPS156 Background: Patients with metastatic colorectal cancer (CRC) often receive intensive platinum-based regimens, such as FOLFOX (fluorouracil [5-FU], leucovorin, oxaliplatin), as first-line (1L) therapy. For patients who do not progress during 1L platinum-based induction therapy, maintenance with a less intensive regimen can enhance clinical benefit and reduce toxicity. The CAIRO3 study showed a progression-free survival (PFS) benefit and a trend toward overall survival (OS) benefit in patients who received maintenance treatment with a fluoropyrimidine and bevacizumab versus observation following induction treatment of six cycles of platinum-based therapy. Olaparib is an oral PARP inhibitor that has efficacy in platinum-sensitive cancers. The randomized, open-label, phase 3 LYNK-003 trial will investigate the efficacy and safety of olaparib, alone or with bevacizumab, compared with bevacizumab plus 5-FU in advanced CRC that has not progressed during 1L induction treatment with FOLFOX plus bevacizumab. Methods: Patients aged ≥18 years with histologically confirmed metastatic or unresectable CRC that has not progressed after 1L induction of ≥6 cycles of FOLFOX plus bevacizumab and who can no longer tolerate oxaliplatin are eligible. Patients must have an ECOG performance status of 0-1, adequate organ function, and provide tumor tissue for biomarker analysis. Patients will be randomly assigned 1:1:1 to olaparib 300 mg twice-daily (BID), olaparib 300 mg BID plus bevacizumab 5 mg/kg every 2 weeks (Q2W), or bevacizumab 5 mg/kg Q2W plus 5-FU 2400 mg/m2 over 46-48 hours Q2W. Randomization will be stratified by response to prior FOLFOX plus bevacizumab (stable disease vs partial response/complete response), mutation status ( BRAFmut and/or Rasmut vs BRAFwt plus Raswt), and number of prior FOLFOX plus bevacizumab cycles (6-8 vs &gt; 8 cycles). Response will be assessed by computed tomography or contrast-enhanced magnetic resonance imaging per RECIST 1.1 by blinded independent central review (BICR) every 8 weeks for the first 12 months and every 12 weeks thereafter. Treatment will continue until documented disease progression, unacceptable toxicity, investigator’s decision to discontinue, or patient withdrawal. The primary endpoint is PFS per RECIST 1.1 by BICR. Secondary endpoints are OS, objective response rate, duration of response, and safety. Approximately 525 patients will be enrolled. Currently, patients are being enrolled at 18 locations in 4 countries. Clinical trial information: NCT04456699.

Cost-utility Analysis of the EOX Drug Regimen versus the DCF Drug Regimen for Patients with Advanced Gastric Cancer

Background: Cancer is one of the major causes of mortality and as an effectivefactor in the burden of diseases for the future. Among all cancers, gastric cancer is thefourth most common and the second leading cause of cancer mortality worldwide. Inthis study, we aim to evaluate the cost-utility of two chemotherapy regimens –epirubicin, oxaliplatin, and capecitabine versus docetaxel, cisplatin, and fluorouracilin patients with advanced gastric cancer in a hospital in southern Iran.Method: This cross-sectional study was an economic evaluation of cost-utility typethat included all patients at Amir Hospital (Shiraz, Iran) who had advanced gastric cancerand received either the epirubicin, oxaliplatin, and capecitabine or docetaxel, cisplatin,and fluorouracil chemotherapy regimen. All costs and the quality-adjusted life yearswere calculated, followed by one-way sensitivity analysis to verify the results.Results:A total of 54 patients participated in this study, amongst whom 20 receivedthe epirubicin, oxaliplatin, and capecitabine regimen and 34 received the docetaxel,cisplatin, and fluorouracil regimen. The mean quality of life of patients that receiveddocetaxel, cisplatin, and fluorouracil was 0.747, whereas it was 0.836 for patients thatreceived epirubicin, oxaliplatin, and capecitabine. The docetaxel, cisplatin, andfluorouracil treatment group ($5573) was more expensive than the epirubicin, oxaliplatin,and capecitabine group ($3108). The results obtained from the cost-utility analysisshowed that the epirubicin, oxaliplatin, and capecitabine drug regimen was costeffectivedue to lower cost and higher utility than the docetaxel, cisplatin, andfluorouracil regimen. One-way sensitivity analysis confirmed the accuracy of theseresults.Conclusion: Due to the cost-effectiveness of the epirubicin, oxaliplatin, andcapecitabine drug regimen compared to docetaxel, cisplatin, and fluorouracil, werecommend that oncologists use this regimen to treat gastric cancer patients.

A retrospective analysis of plasma concentration monitoring of fluorouracil in patients with advanced colorectal cancer

ObjectivesTo analyse the results of fluorouracil (5-FU) plasma concentration monitoring in patients with advanced colorectal cancer after 5-FU treatment, and to provide a reference for the application prospect of 5-FU...

Induction Chemotherapy with Paclitaxel Liposome, Nedaplatin, and Fluorouracil in Patients with Locally Advanced Nasopharyngeal Carcinoma: A Phase II Study

A previous study found that adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy could improve failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma (NCT01245959). Paclitaxel liposome may have fewer side effects and work better than paclitaxel. Nedaplatin, a cisplatin analog, has been developed to decrease the toxicities induced by cisplatin, such as nephrotoxicity and gastrointestinal toxicity. In this study, we aimed to evaluate the safety and efficacy of induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil in patients with locally advanced nasopharyngeal carcinoma. In total we included 46 patients with newly diagnosed and pathologically confirmed stage III-IV nonkeratinized nasopharyngeal carcinoma in Nanjing University affiliated Drum Tower Hospital from 2015 May to 2017 June. Patients were treated with paclitaxel Liposome (135mg/m2), nedaplatin (60mg/m2), and fluorouracil (600mg/m2/day×5days), every 3 weeks for 2 cycles. If patients achieved partial response (PR) or complete response (CR) according to the RECIST criteria 1.0, another cycle was then added. Radiotherapy plus concurrent chemotherapy with nedaplatin was subsequently given with a total dose of 70Gy-74Gy with 2Gy per fraction in 35-37 fractions. Treatment response was evaluated 1 month after the end of the treatment. If patients achieved PR or CR, the treatment was consequently ended. The median age of studied patients was 50 years old (range, 25-74 years). Twenty-eight patients (60.9%, 28/46) had stage III disease, nine (19.6%, 9/46) had stage IVa disease and nine patients (19.6%, 9/46) were with stage IVb disease. Thirty-eight patients completed 3 cycles induction chemotherapy (80.1%, 38/47). CTCAE version 4.0 was referred to grade treatment-related toxicities. Three patients (6.5%, 3/46) developed grade 3 bone marrow suppression. Grade 1 nausea occurred in 3 patients (6.5%, 3/46) and grade 1 malaise occurred in 5 patients (10.9%, 5/46). After the induction chemotherapy, no patients achieved CR, 37 patients (80.4%, 37/46) achieved PR, 8 patients (17.4%, 8/46) were with stable disease (SD) and 2 patients (4.3%, 2/46) developed progressive disease (PD) (PR in primary tumor but with lung metastases). After induction chemotherapy plus concurrent chemoradiotherapy, all the patients achieved PR or CR. The median follow-up was 16 months (range, 8-33 months). Distant metastases occurred in 9 patients (5 patients with lung metastasis, 2 with bone metastasis, 2 with liver metastasis), and only 1 patient had in-field recurrence. Induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil is safe and efficient for patients locally advanced nasopharyngeal carcinoma. This regimen is well tolerated and might be especially helpful for patients with poor performance status. The long-term survival will be updated in future.

Induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil in patients with locally advanced nasopharyngeal carcinoma: A phase II study.

e18024Background: A previous study found that adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy could improve failure-free survival in patie...

Capecitabine in locally advanced anal cancer, do we need randomised evidence?

ABSTRACTIntroduction: Standard treatment for locally advanced anal cancer is chemoradiotherapy with mitomycin C and fluorouracil. However, infusional fluorouracil requires central venous catheter placement potentiating risk of infection and thrombosis. Capecitabine which is an oral tumor activated fluoropyrimidine carbamate is an established treatment alternative to infusional fluorouracil for patients with gastrointestinal cancers.Areas covered: This review examines and discusses the current evidence for substitution of Capecitabine for infusional fluorouracil in locally advanced anal cancer. Two phase II studies, one phase I study and three retrospective reviews were identified. The rate of complete response and locoregional control with the use of Capecitabine in all of these studies ranged from 77% to 89.1% and 79% to 94% respectively, and these results are comparable with prior pivotal studies. The main toxicity with radiation and Capecitabine is radiation dermatitis occurring in 23% to 63% of patients. Despite high rates of radiation dermatitis, treatment completion rates were high, suggesting that it is a well tolerated protocol.Expert commentary: Capecitabine has been used widely in other gastrointestinal cancers, including rectal cancer in chemo-radiotherapy protocols, with proven efficacy and safety and could be a reasonable treatment alternative to fluorouracil in locally advanced anal cancer.

Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy

KRAS mutations are common in pancreatic cancer, but directly targeting the KRAS protein has thus far been unsuccessful. The aim of this trial was to block the MEK and PI3K/AKT pathways downstream of the KRAS protein as an alternate treatment strategy to slow cancer growth and prolong survival. This was the first cooperative group trial to evaluate this strategy using molecularly targeted oral combination therapy for the treatment of chemotherapy-refractory pancreatic cancer. To compare selumetinib and MK-2206 vs modified FOLFOX (mFOLFOX) in patients with metastatic pancreatic cancer for whom gemcitabine-based therapy had failed. SWOG S1115 was a randomized phase 2 clinical trial. Between September 2012 and May 2014, 137 patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed were randomized to selumetinib plus MK-2206 or mFOLFOX. Patients were randomized in a 1:1 fashion and stratified according to duration of prior systemic therapy and presence of liver metastases. Patients received selumetinib 100 mg orally per day plus MK-2206 135 mg orally once per week or mFOLFOX (oxaliplatin, 85 mg/m2 intravenous, and fluorouracil, 2400 mg/m2 intravenous infusion over 46-48 hours) on days 1 and 15 of a 28-day cycle. The primary end point of the study was overall survival. Secondary objectives included evaluating toxic effects, objective tumor response, and progression-free survival. There were 58 patients in the selumetinib plus MK-2206 (experimental) arm (60% male; median [range] age, 69 [54-88] years) and 62 patients in the mFOLFOX arm (35% male; median [range] age, 65 [34-82] years). In the experimental arm, median overall survival was shorter (3.9 vs 6.7 months; HR, 1.37; 95% CI, 0.90-2.08; P = .15), as was median progression-free survival (1.9 vs 2.0 months; HR, 1.61; 95% CI, 1.07-2.43; P = .02). One vs 5 patients had a partial response and 12 vs 14 patients had stable disease in the experimental arm vs mFOLFOX arm. Grade 3 or higher toxic effects were observed in 39 patients treated with selumetinib and MK-2206 vs 23 patients treated with mFOLFOX. More patients in the experimental arm discontinued therapy due to adverse events (13 vs 7 patients). Dual targeting of the MEK and PI3K/AKT pathways downstream of KRAS by selumetinib plus MK-2206 did not improve overall survival in patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed. This was the first randomized prospective evaluation of mFOLFOX in the US population that showed comparable results to CONKO-003 and PANCREOX. clinicaltrials.gov Identifier: NCT01658943.

Efficacy and safety of rhLTα-Da with cisplatin and fluorouracil in patients with metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open-labelled, controlled, phase IIb trial.

4036Background: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is the LTα derivative without N-terminal 27 amino acid residues. Our prior studies showed that the addition of rhLTα-Da to cisp...

Capecitabine maintenance after first-line induction chemotherapy with docetaxel, cisplatin, and fluorouracil in patients with advanced gastric cancer.

e15003 Background: Chemotherapy improves the survival of patients with advanced gastric cancer, but patient survival remains less than 12 months despite optimal treatment. Maintenance therapy after...

P16 Methylation is associated with chemosensitivity to fluorouracil in patients with advanced gastric cancer.

No effective biomarkers have been confirmed to predict chemosensitivity for patients with gastric cancer. The purpose of this study was to investigate whether DNA methylation is associated with chemosensitivity in patients with gastric cancer. Tumors and matched non-tumor biopsy tissues collected from 134 advanced gastric cancer (AGC) patients prior to fluorouracil-based chemotherapy were retrospectively analyzed. The methylation status of p16, E-cadherin (CDH1), MGMT (O-6-methylguanine-DNA methyltransferase), and human mutL homolog 1 (hMLH1) was evaluated using a Methylight assay, and the association between p16 methylation and the sensitivity of 5-fluorouracil in cell lines was determined by in vitro assay. The methylation of p16 (17.9 vs. 0 %, P = 0.002), CDH1 (20.9 vs. 2.2 %, P < 0.001), MGMT (17.9 vs. 0 %, P = 0.052), and hMLH1 (14.9 vs. 2.2 %, P = 0.024) was more common in gastric cancer tissues (n = 134) than in non-tumor tissues (n = 46). For all patients, a reverse correlation was only found between p16 methylation and clinical response (P = 0.017), which suggested that p16 methylation might be associated with chemosensitivity of fluorouracil in gastric cancer patients. Results from in vitro experiments demonstrated that p16 methylation was closely correlated with the sensitivity of 5-fluorouracil in gastric cancer cells. The present results indicated that the methylation of p16, CDH1, MGMT, and hMLH1 was both frequent and specific in gastric cancer tissues. p16 Methylation might be used to predict chemosensitivity of fluorouracil for patients with AGC when validated in large samples in the future.

Comparison of preoperative chemotherapy using docetaxel, cisplatin and fluorouracil with cisplatin and fluorouracil in patients with advanced carcinoma of the thoracic esophagus

We retrospectively compared preoperative docetaxel, cisplatin, and fluorouracil (DCF) with cisplatin and fluorouracil (CF) in patients with esophageal cancer. The study included patients with advanced thoracic esophageal carcinoma (excluding T4 tumors) receiving preoperative chemotherapy. In the DCF group, five patients received two courses of treatment every 4 weeks, and 33 patients received three courses every 3 weeks. In the CF group, 38 patients received two courses of treatment every 4 weeks. Patients underwent curative surgery 4-5 weeks after completing chemotherapy. Patient demographic characteristics did not differ between the two study groups. The incidence of a grade 3 or 4 hematologic toxicity was significantly higher in the DCF group (33 patients) than in the CF group (five patients; P < 0.001). Curative resection was accomplished in 79% of patients in the DCF group and 66% in the CF group (P = 0.305). There were no in-hospital deaths. The incidence of perioperative complications did not differ between the groups. A grade 2 or 3 histological response was attained in a significantly higher proportion of patients in the DCF group (63%) than in the CF group (5%; P < 0.001). Progression-free survival and overall survival were significantly higher in the DCF group (P = 0.013, hazard ratio 0.473; P = 0.001, hazard ratio 0.344). In conclusion, a grade 3 or 4 hematologic toxicity was common in the DCF group but was managed by supportive therapy. Histological response rate, progression-free survival, and overall survival were significantly higher in the DCF group compared with the CF group.

Prognostic factors for anti-cancer therapy efficiency

Aim. To investigate the relationship between blood plasma biochemical indicators in patients with solid tumors before a treatment and after the first course of chemotherapy with objective treatment response. Methods. Blood plasma samples taken from 14 patients with cancer relapse were studied before the treatment and after the first course of specific chemotherapy (carboplatin, methotrexate, vinblastine in patients with urine bladder cancer and irinotecan, leukovorin and fluorouracil in patients with colorectal cancer). The first group included patients with colorectal cancer relapse (males - 3, females - 4) aged 57-62 years. The second group included patients with urine bladder cancer relapse (males - 5, females - 2) aged 48-64 years. Free radical activity and protein oxidative modification, as well as endogenous intoxication and major mineral and trace elements levels were studied. Results. When achieving the objective chemotherapy effect in patients after the first treatment course, an increase of alpha-1 globulin and gamma globulin level, as well as an increase of phosphorus, zinc, lithium and iron blood plasma level was observed. In case of following disease progression, the opposite dynamics of above-mentioned indicators was revealed. In patients with good objective effect of polychemotherapy after the first treatment course, a significant increase of endogenous intoxication and blood plasma free radical activity decrease were observed. If the following tumor progression was observed, the tendency of blood plasma free radical activity increase, accompanied by the total protein oxidative modification activation, was revealed after the first treatment course. Conclusion. The increase of alpha-1 and gamma globulin levels, as well as an increase of phosphorus level in blood plasma after the first course of polychemotherapy can be used as prognostic factors of anticancer therapy efficiency. High level of endogenous intoxication as well as an increase of copper, iron, zinc and lithium blood plasma concentrations can be applied as the additional markers.

Concurrent chemoradiation with cisplatinum versus cisplatinum and fluorouracil in patients with cervical cancer

Concurrent chemoradiation with cisplatinum versus cisplatinum and fluorouracil in patients with cervical cancer

Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial

Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma. In this single blind, non-inferiority, randomised controlled multicentre trial, we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherlands. Patients were randomly assigned to receive treatment with methylaminolevulinate photodynamic therapy (MAL-PDT; two sessions with an interval of 1 week), imiquimod cream (once daily, five times a week for 6 weeks), or fluorouracil cream (twice daily for 4 weeks). Follow-up was at 3 and 12 months post-treatment. Data were collected by one observer who was blinded to the assigned treatment. The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up. A pre-specified non-inferiority margin of 10% was used and modified intention-to-treat analyses were done. This trial is registered as an International Standard Randomised controlled trial (ISRCTN 79701845). 601 patients were randomised: 202 to receive MAL-PDT, 198 to receive imiquimod, and 201 to receive fluorouracil. A year after treatment, 52 of 196 patients treated with MAL-PDT, 31 of 189 treated with imiquimod, and 39 of 198 treated with fluorouracil had tumour residue or recurrence. The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8% (95% CI 66.8-79.4) for MAL-PDT, 83.4% (78.2-88.9) for imiquimod cream, and 80.1% (74.7-85.9) for fluorouracil cream. The difference between imiquimod and MAL-PDT was 10.6% (95% CI 1.5-19.5; p=0.021) and 7.3% (-1.9 to 16.5; p=0.120) between fluorouracil and MAL-PDT, and between fluorouracil and imiquimod was -3.3% (-11.6 to 5.0; p=0.435. For patients treated with MAL-PDT, moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session. For other local adverse reactions, local skin redness was most often reported as moderate or severe in all treatment groups. Patients treated with creams more often reported moderate to severe local swelling, erosion, crust formation, and itching of the skin than patients treated with MAL-PDT. In the MAL-PDT group no serious adverse events were reported. One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting. Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma. On the basis of these findings, imiquimod can be considered the preferred treatment, but all aspects affecting treatment choice should be weighted to select the best treatment for patients. Grant of the Netherlands Organization for Scientific Research ZONMW (08-82310-98-08626).

Combination chemotherapy with paclitaxel, cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma: a multicenter prospective study

To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU (PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction (EGJ) adenocarcinoma in China. The patients were treated with paclitaxel 150 mg/m2 on d1; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/(m2·d) intravenously on d1–d5 of a 21-d cycle until disease progression or unacceptable toxicities. Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy (group A) and 34 received the regimen as the second-line therapy (group B) with the median age of 59 years old and Karnofsky performance status (KPS) score ≥80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival (mOS) was 12.0 months (95% CI: 7.9–16.2 months) in group A and 7.3 months (95% CI: 4.3–10.3 months) in group B, respectively. The median progression-free survival (mPFS) was 5.7 months (95% CI: 4.1–7.2 months) and 5.0 months (95% CI: 3.1–6.9 months), respectively. The response rate (CR+PR) was 40% (16/40; 95% CI: 24.9–56.7%) in group A and 22.6% (7/31; 95% CI: 9.6–41.1%) in group B. Major grade 3 or 4 adverse events include neutropenia (41.3%), febrile neutropenia (9.3%), nausea/anorexia (10.7%), and vomiting (5.3%). There was no treatment-related death. The combination chemotherapy with PCF is active and tolerable as first-line and secondline therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.