Epirubicin, Cisplatin, Fluorouracil Research Articles

Updated Adjuvant Chemotherapy for Gastric Cancer.

Surgical resection is currently the best curative approach for gastric cancer (GC); however, the prognosis of patients with advanced GC remains poor even with curative resection. For this reason, perioperative chemotherapy has been combined with surgery to reduce the risk of postoperative recurrence. Standard perioperative chemotherapy for resectable advanced GC varies from region to region. Postoperative S-1 therapy was standardized via the ACTS-GC study in East Asia, perioperative ECF (Epirubicin + Cisplatin + Fluorouracil) was standardized via the MAGIC study in Europe, and postoperative chemoradiotherapy was standardized via the US intergroup study in North America. Since then, more intensive regimens have been developed. In recent years, perioperative therapy using novel agents, such as molecular-targeted drugs and immune checkpoint inhibitors (ICIs), has also been tested and evaluated in the three major regions (East Asia, Europe, and North America) with promising results. Perioperative chemotherapy has become an integral part of many treatment strategies and requires continued research and evaluation.

Efficacy and safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as perioperative chemotherapy treatments for resectable gastric cancer patients; a report from the middle east.

This study aimed to compare the efficacy and toxicity of perioperative chemotherapy regimens including epirubicin, cisplatin, 5-fluorouracil (ECF), docetaxel, cisplatin, 5-fluorouracil (DCF), leucovorin, 5-fluorouracil, oxaliplatin (FOLFOX), and 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) to identify the most effective chemotherapy regimen with less toxicity. This retrospective cohort study (2014-2021) was based on 152 eligible resectable gastric cancer patients who had received one of the perioperative mentioned chemotherapy regimens and followed for at least two years. The primary endpoint of this study was overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and R0 resection. Of included patients, 21%, 33.7%, 24.3%, and 21% had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 30-month follow-ups, OS was higher with the FLOT regimen in comparison with other regimens (hazard ratio = 0. 276). The median OS of the FLOT regimen was 39 months. Besides, the median OS was 28, 25, and 21 months for DCF, FOLOFX, and ECF regimens, respectively. Moreover, a median PFS of 24, 18, 17, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank < 0.001). FLOT regimen showed 84. 4% ORR which was notably higher than other groups. For resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients' OS and PFS versus ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered the optimal option for managing resectable gastric cancer patients.

The cytotoxic effects of green synthesized AgCl2 nanoparticles on gastric cancer (AGS) cells

In recent years, with the development of nanotechnology, the use of various metal nanoparticles has become widespread specifically in the treatment of cancer. Furthermore, the application of silver nanoparticles (AgNPs) should not be denied in this respect. AgNPs hold great potential in the field of cancer biology and because of their anti-microbial activities they are vastly used in diverse clinical applications. AgNPs possess some physical and chemical features including heterogeneity in size, shape, and capping material. Moreover, their novel cytotoxic characteristics against mammalian cells makes them more applicable in tumor therapy and acting as anti-cancer agents. AgNPs have great potential in tumor diagnosis as well as treatment (Zhao et al., 2022; Păduraru et al., 2022; Patil et al., 2021). Gastric cancer is the fifth most common cancer with more than 1 million people newly diagnosed worldwide each year. Despite its worldwide decline in incidence and mortality over the past 5 decades, gastric cancer remains the third leading cause of cancer-related death (Sexton et al., 2020; Thrift and El-Serag, 2020) Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Metastatic gastric cancer remains a non-curative disease. Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. In the setting of metastatic or inoperable gastric cancer, the current evidence shows that chemotherapy improves survival in comparison to best supportive care and that combination chemotherapy is superior to monotherapy in terms of survival, response rate and symptom control. Although there are no internationally accepted standard regimens, in Europe, ECF (epirubicin, cisplatin, fluorouracil) has been considered the reference regimen; in the US cisplatin-fluoropyrimidine combinations are mainly used, while in Japan, cisplatin with S1 has become the standard. It has also been suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line). Gastrointestinal symptoms are the most notable side effects of chemotherapeutic drugs (Kim et al., 2013; Janunger et al., 2001; Choi et al., 2018; Sastre et al., 2006; Zhou et al., 2017). Many recent studies have shown that green synthesized silver nanoparticles (AgNPs) can have cytotoxic effects on different cancer cells (Yesilot and Aydin, 2019). The biosynthesized AgNPs using the leaves extracts of Hemichroa pentandra showed considerable antioxidant activity and excellent anti-cancer activity against breast cancer cells (Punathil, 2018). Biosynthesized AgNPs from the leaf extract of Ochradenus arabicus can have suppressive effects against the human breast cancer cells (Al-kawmani et al., 2020). Also, green synthesized silver nanoparticles using Teucrium polium leaf extract exhibited significant anticancer activity against MNK45 human gastric cancer cell line (Hashemi et al., 2020). In this study we investigated the cytotoxic effects of green synthesized AgCl2 nanoparticles on gastric cancer (AGS) cells. Onopordum acanthium extract was used to synthesize AgCl2 nanoparticles. Onopordum acanthium has been applied traditionally as bactericide and antitumor agent (Al-Snafi, 2020). Gastric cancer cells were purchased from Pasteur Institute of Iran and cultured in growth medium until they reached 80-90% confluence. The cells were then treated with different concentrations (1.5625, 3.125, 6.25, 12.5, 25 and 50 μg/ml) of AgCl2 nanoparticle for 24 hours. The cytotoxic effect of AgCl2 nanoparticles was assessed using MTT assay method. The results showed that viability of AGS cells did not significantly change 24 hours after treatment with 1.5625 μg/ml of green synthesized AgCl2 nanoparticles compared to the control group; However, the viability in AGS cells significantly decreased when treated with 3.125, 6.25, 12.5, 25 and 50 μg/ml of green synthesized AgCl2 nanoparticles compared to control group. There cytotoxic effect was more in groups treated with 6.25, 12.5, and 25 than groups treated with 3.125, 6.25, and 12.5 μg/ml of green synthesized AgCl2, respectively. There was not significant difference between cell viability of group treated with 25 and 50 μg/ml of green synthesized AgCl2.Conclusion: Our results show that green synthesized AgCl2 nanoparticles have cytotoxic effects against gastric cancer (AGS) cells in vitro.

Radiotherapy patterns of care in gastric adenocarcinoma: a single institution experience.

Gastric adenocarcinoma (GAC) is one of the most commonly diagnosed cancers worldwide. Two standard approaches for treatment of resectable GAC include adjuvant 5-fluorouracil-based chemoradiotherapy [per Intergroup 0116 (INT-0116) trial and perioperative epirubicin, cisplatin, fluorouracil (ECF) chemotherapy per Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial]. Controversy remains regarding the most appropriate treatment strategy to decrease recurrence rates and improve survival following surgery. The purpose of this study was to analyze how patterns of care for patients with GAC treated at Emory University Hospital changed following publication of the MAGIC trial in 2006. We analyzed a prospectively maintained database of 150 patients who underwent resection for GAC between December 2000 and June 2013. Patients were divided into two cohorts, Early [2000-2006] and late [2007-2013]. The primary objective was to compare the number of patients assigned to adjuvant chemoradiotherapy (aCRT) vs. perioperative chemotherapy (PC) throughout the study period and secondarily assess for recurrence patterns and survival outcomes for patients assigned to those two strategies. Between 2000 and 2013, 124 patients received adjuvant therapy for GAC. Fifty-four patients were treated with PC and 70 patients with aCRT. The early cohort included 56 patients, and the late cohort included 94 patients. There was no statistical difference in the number of patients receiving aCRT between the Early and Late cohorts [n=23 (50%) vs. 35 (38%) respectively, P=0.21]. PC increased from 2 patients (3.6%) in the Early cohort to 32 patients (34%) in the Late cohort (P<0.001). Four-year overall survival (OS) was 32.6% for the Early cohort and 68.8% for the Late cohort (P=0.010). Overall recurrence rate was 25.3% with no significant difference in rates of recurrence seen between the Early and Late cohorts. PC has become more prevalent in patients treated at Emory following publication of the MAGIC trial in 2006. OS, but not recurrence rates, has also improved since publication. Although improved survival is suggestive of improved care, the question of optimal treatment regimen remains open. Further prospective comparisons of PC and aCRT are needed to identify patient and disease parameters that may guide therapy selection.

A retrospective study of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) for locally advanced gastric or gastro-esophageal junction adenocarcinoma (GC).

138 Background: Perioperative chemotherapy (chemo) with ECF (epirubicin/cisplatin/5-fluorouracil) plus surgery improved survival over surgery alone in GC in the MAGIC trial. Herein we report our experience using DCF in the perioperative setting in patients (pts) with locally advanced GC. Methods: We conducted a retrospective IRB-approved study of pts with potentially resectable locally advanced GC who were treated with DCF with neoadjuvant intent. Pts received 3 cycles of preoperative (pre-op) DCF every 3 weeks, followed by surgery, then 3 cycles of postoperative (post-op) DCF. Patients with a poor pathologic response could be changed to radiation (RT) or an alternate chemo regimen postop. Results: A total of 41 pts were identified, 24 with gastric and 17 with GEJ adenocarcinoma. All pts received at least 1 cycle of DCF and 78% received at least 3 cycles pre-op. Five pts progressed during neoadjuvant DCF, 4 were unresectable by CT after neoadjuvant DCF and 2 were lost to follow-up. The remaining 30 pts had surgery with curative intent. Post-op, 2 pts were lost to follow-up, 12 received DCF (with 6 of these also receiving RT), 11 received a different chemo regimen due to a poor response to neoadjuvant DCF (including 6 pts who also received RT). Two pts received post-op RT only. The median PFS was 16.8 months (95% CI 7.7 - 25.9) and the median OS was 26.9 months (95% CI 18.7–35.1). The PFS was longer for pts who had a radiological or pathological response to neoadjuvant DCF (log rank p = 0.005 and 0.02 respectively) and for pts who received DCF post-op (log rank p = 0.005). Among pts who did not receive DCF post-op, there was no survival difference between the pts who were switched to an alternative chemo or chemoRT regimen post-op compared to those who received no further therapy. The most common chemo-related adverse events were anemia (27% grade 3 or 4), nausea/vomiting (17% G3 or 4), and febrile neutropenia (12%). Conclusions: The DCF regimen is well tolerated in locally advanced GC. Patients who do not have a good response (either radiologic or pathologic) to pre-op DCF appear to have a poor prognosis regardless of the post-op treatment given.

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m(2) epirubicin on day 1, 60 mg/m(2) cisplatin for 2 h on day 2, and 500 mg/m(2) 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD). The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm(3) (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-II (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm(3) and good prognostic factors.

Clinicopathologic Characteristics and Survival Outcomes of Patients with Advanced Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma: A Single-Institution Experience

Most patients with gastric or gastroesophageal junction (gej) cancer are diagnosed with inoperable advanced or metastatic disease. In these cases, chemotherapy is the only treatment demonstrating survival benefit. The present study compares clinicopathologic characteristics and survival outcomes for patients with advanced esophageal, gej, and gastric adenocarcinoma treated with first-line chemotherapy [epirubicin-cisplatin-5-fluorouracil (ecf), epirubicin-cisplatin-capecitabine (ecx), or etoposide-leucovorin-5-fluorouracil (elf)] or best supportive care (bsc) at our institution with those for historical controls. We retrospectively reviewed medical information for 401 patients with newly diagnosed advanced esophageal, gej, or gastric adenocarcinoma treated with first-line chemotherapy (ecf, ecx, or elf) or bsc from January 1, 2004, through December 31, 2010. Descriptive statistics were used to compare the data collected with data for historical control patients. Of the study patients, 93% were diagnosed with metastatic disease (n = 374), and 63% received bsc only (n = 251). The main reasons that patients received bsc only included poor Eastern Cooperative Oncology Group performance status (55%), patient decision (31%), and comorbidities (14%). Of the remaining patients, 98 (24%) received ecf or ecx and 52 (13%) received elf as first-line treatment. Median overall survival was significantly longer in patients treated with ecf or ecx or with elf than in those receiving bsc (12.7 months vs. 12.7 months vs. 5.5 months respectively). Chemotherapy also significantly reduced the risk of death (64% reduction with ecf or ecx, 58% with elf). We confirmed the substantial overall survival benefit of combination chemotherapy compared with bsc, with better survival in our patient population than in historical controls. However, novel treatment options are still warranted to improve outcomes in this patient population.

Neoadjuvant or adjuvant therapy for resectable gastric cancer: a systematic review and practice guideline for North America

Gastric cancer is a global health problem accounting for 10% of all new cancer cases and 12% of all cancer deaths worldwide. Many clinical trials and meta-analyses have explored the value of neoadjuvant or adjuvant chemotherapy and radiation therapy in gastric cancer; however, these studies have produced conflicting results. The purpose of this guidance document was to determine whether patients with resectable gastric cancer should receive neoadjuvant or adjuvant therapy in addition to surgery. Outcomes of interest were overall survival, disease-free survival, and adverse events. A systematic review was undertaken to inform recommendations regarding neoadjuvant and adjuvant therapy in resectable gastric cancer in Ontario, Canada. MEDLINE and EMBASE databases, as well as American Society of Clinical Oncology (ASCO) annual meeting proceedings and American Society for Therapeutic Radiology and Oncology (ASTRO) proceedings were systematically searched from 2002 to 2010. Oral fluoropyrimidine trials were excluded owing to the unavailability of these agents in North America. Overall, 22 randomized controlled trials (RCTs), 13 meta-analyses, and two secondary analyses were included. The systematic review informed the development of a clinical practice guideline with the following recommendations. Postoperative 5-fluorouracil-based chemoradiotherapy based on the Macdonald approach or perioperative ECF (epirubicin, cisplatin, fluorouracil) chemotherapy based on the Cunningham/MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) approach are both acceptable standards of care in North America. Choice of treatment should be made on a case-by-case basis. Adjuvant chemotherapy is a reasonable option for those patients for whom the Macdonald and MAGIC protocols are contraindicated. All patients with resectable gastric cancer should undergo a pretreatment multidisciplinary assessment to determine the best plan of care. Overall survival in patients with resectable gastric cancer is significantly improved with the use of either postoperative chemoradiation (Macdonald approach) or perioperative ECF (MAGIC protocol).

CALGB 80403/ECOG 1206: A randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer.

4006 Background: ECF (epirubicin, cisplatin, fluorouracil), IC (irinotecan, cisplatin), and FOLFOX (leucovorin, fluorouracil, oxaliplatin) are commonly used regimens for esophagogastric cancer. Cetuximab (C) improves the antitumor activity of platinum-based-therapy in head and neck and colorectal cancer. KRAS is mutated in 2% of esophageal cancers. Methods: Patients (pts) with chemonaive, metastatic, measurable adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of the esophagus (E) or GE junction (GEJ) were randomized to 3 regimens: (A) epirubicin 50 mg/m2/d1, cisplatin 60 mg/m2/d1, 5-FU 200 mg/m2/d1-21 q 21d; (B) irinotecan 65 mg/m2/d1, 8, cisplatin 35 mg/m2/d1, 8 q 21d; (C) oxaliplatin 85 mg/m2/d1, leucovorin 500 mg/m2/d1, 5-FU 500 mg/m2/d1, 5-FU 1,200 mg/m2/d1-2 q 14d. Pts were stratified by histology-ADC vs. SCC and ECOG performance status—0 and 1 vs. 2. With 64 measurable ADC pts treated per regimen, the study had a 90% power (1-sided) to detect an improvement in major response from 25% to 40%. Re...

Docetaxel, Cisplatin, and Fluorouracil; Docetaxel and Cisplatin; and Epirubicin, Cisplatin, and Fluorouracil As Systemic Treatment for Advanced Gastric Carcinoma: A Randomized Phase II Trial of the Swiss Group for Clinical Cancer Research

This randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy. Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric carcinoma, a performance status <or= 1, and adequate hematologic, hepatic, and renal function randomly received <or= eight 3-weekly cycles of ECF (epirubicin 50 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and fluorouracil [FU] 200 mg/m(2)/d on days 1 to 21), TC (docetaxel initially 85 mg/m(2) on day 1 [later reduced to 75 mg/m(2) as a result of toxicity] and cisplatin 75 mg/m(2) on day 1), or TCF (TC plus FU 300 mg/m(2)/d on days 1 to 14). Study objectives included response (primary), survival, toxicity, and quality of life (QOL). ORR was 25.0% (95% CI, 13% to 41%) for ECF, 18.5% (95% CI, 9% to 34%) for TC, and 36.6% (95% CI, 23% to 53%) for TCF (n = 119). Median overall survival times were 8.3, 11.0, and 10.4 months for ECF, TC, and TCF, respectively. Toxicity was acceptable, with one toxic death (TC arm). Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel (TC, 49%; TCF, 57%; ECF, 34%). Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens. Time to response and ORR favor TCF over TC for further evaluation, particularly in the neoadjuvant setting. A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed.

Primary therapy with ECF in combination with a GnRH analog in premenopausal women with hormone receptor-positive T2–T4 breast cancer

Patients with hormone receptor-positive tumors less often show a pathological complete response (pCR) than do those with hormone receptor-negative tumors. The addition of endocrine therapies may improve the clinical benefits of primary therapies in these patients. We investigated the efficacy of the epirubicin+cisplatin+fluorouracil (ECF) as continuous infusion) regimen in association with a gonadotropin-releasing hormone (GnRH) analog in 36 premenopausal women with T2-T4a-d N0-2 M0 ER and/or PgR-positive breast cancer. Median age was 39.5 years (range 26-53). Clinical response (complete or partial) was observed in 27 out of 36 patients (75% 95% CI 57.8-87.9%) and a pCR was observed in four patients (11%). Nine (25%) patients had stable disease and no progression was observed. Twenty-one patients (58%) were submitted for breast-conserving surgery and 15 had a radical mastectomy. No baseline clinical and biological characteristics significantly correlated with response. Thirty out of 31 patients evaluable for endocrine assessment had documented ovarian suppression, which occurred after a median of 28 days (range 20-43). We conclude that the combination of ECF and a GnRH analog is associated with a high response rate in the primary treatment of breast cancer. Further studies combining chemotherapy and endocrine agents are warranted in patients with hormone receptor-positive tumors.

Is oxaliplatin the optimal platinum agent in gastric cancer?

Epirubicin-cisplatin-5-fluorouracil (ECF) is commonly used to treat advanced gastric cancer. Two new cytotoxic agents: the platinum, oxaliplatin, and the oral fluoropyrimidine, capecitabine, have the potential to replace the cisplatin and 5-fluorouracil (5-FU) components of ECF, respectively. Oxaliplatin showed anti-tumour activity in human gastric cancer cell lines and was active in Phase II studies in advanced gastric cancer. Using ECF as a reference regimen, the Phase III REAL-2 study compared oxaliplatin with cisplatin, and capecitabine with 5-FU in patients with previously untreated, locally advanced or metastatic cancer of the oesophagus, gastro-oesophageal junction or stomach. The results of this study indicate that oxaliplatin and capecitabine could replace the platinum and fluoropyrimidine components of ECF, with no adverse effect on efficacy, improved convenience and favourable safety. Further trials of oxaliplatin in combination with other cytotoxics may result in novel active regimens in this disease.

Randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric (OG) cancer: The REAL 2 trial

LBA4017 Background: The aim was to establish the potential use of the third generation platinum compound, oxaliplatin (O) &amp; the oral fluoropyrimidine capecitabine (X) in untreated patients (pts) with advanced OG cancer. Methods: After stratification for PS and extent of disease, pts with histologically confirmed adenocarcinoma, squamous or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction or stomach were randomised, in a 2 x 2 design, to 1 of 4 regimens; epirubicin, cisplatin, fluorouracil (ECF), EOF, ECX or EOX. Doses E 50 mg/m2, C 60 mg/m2 &amp; O 130 mg/m2 IV 3 weekly; F 200 mg/m2 IV daily &amp; X 625 mg/m2 twice daily PO continuously; for 8 cycles. The primary endpoint was overall survival. With 1000 pts (250 per arm) the study had 80% power to demonstrate non-inferiority of X over F and also O over C if the upper limit of the HR 95% CI excluded 1.23 (α = 0.05) in the per protocol population. Analysis was performed using the logrank test and Cox regression analysis. Results: 1002 pts were randomised from 61 centres. Demographics were balanced, 89% were PS 0–1, 77% metastatic, median age 63 (range 22–83), 81% were male and 40% gastric primaries. Histology: adenocarcinoma in 88% and 52% poorly differentiated. 11 pts were ineligible and 27 pts were withdrawn before treatment commenced. Median follow up was 17.1 months and 850 events have occurred. There were no significant differences in response rates comparing ECF to, EOF, ECX and EOX (41%, 42%, 46%, and 48% respectively); grade 3–4 non haematological toxicity 36%, 42%, 33% and 45%; and grade 3–4 neutropaenia 42%, 30% (p = 0.008), 51% (p = 0.043) and 28% (p = 0.001) respectively. Conclusions: Capecitabine may replace 5FU and Oxaliplatin may replace Cisplatin in triplet regimens used for the treatment of advanced OG cancer. [Table: see text] [Table: see text]

Cancer cell adaptation to chemotherapy

BackgroundTumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors.MethodsCells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels.ResultsIn 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors.ConclusionThis study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.

Systemic treatment of gastric cancer.

Gastric cancer is one of the commonest cancers worldwide and is associated with a poor prognosis. Surgery remains the only potentially curative treatment, but is associated with a high rate of locoregional recurrence. Hence, there is ongoing debate regarding both the extent of lymph node dissection and the role of perioperative chemotherapy or chemoradiation for localized disease. Untreated metastatic gastric cancer is associated with a median survival of only 3-4 months, but this can be increased to 8-10 months, associated with improved quality of life, with combination chemotherapy. Currently, no standard combination chemotherapy regimen exists, although regimens utilizing both cisplatin and 5-fluorouracil, such as epirubicin/cisplatin/fluorouracil (ECF), are amongst the most active. Newer chemotherapeutic agents, including irinotecan, oxaliplatin and taxanes, show promising activity, and are currently being tested in phase III trials.