Cetuximab in combination with cisplatin and docetaxel as first-line treatment in patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Italian phase II DOCETUX study)

Pinto, Carmine; Fabio, Francesca Di; Barone, C.; Siena, Salvatore; Falcone, Alfredo; Llimpe, F. L. Rojas; Cascinu, S.; Giaquinta, S.; Schinzari, Giovanni; Mutri, V.; Martoni, Andrea

doi:10.1200/jco.2008.26.15_suppl.4575

Cited by 13 publications

(10 citation statements)

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“…Although a study to evaluate a combination of docetaxel with cetuximab (400 mg/m 2 initial dose followed by 250 mg/m 2 weekly for maintenance) with docetaxel (30 mg/m 2 on days 1 and 8 every 3 weeks) in a salvage treatment setting suggested it had limited clinical benefi t in terms of ORR, PFS, and OS [68], the incorporation of cetuximab (400 mg/m 2 initial dose followed by 250 mg/m 2 weekly for maintenance) into a doublet docetaxel regimen (DOCETUX; docetaxel 75 mg/m 2 and CDDP 75 mg/m 2 every 3 weeks) showed hopeful results, with an ORR of 40.5% (one complete response) in the front-line setting [69]. The most common grade III/IV toxicities were neutropenia (45.8%), febrile neutropenia (22.9%), and anemia (6.25%); toxicities included fatigue (22.9%), hyponatremia (20%), hypokalemia (16%), skin reaction (31.3%), vomiting (8.3%), and stomatitis (6.3%).…”

Section: Combinations With Irinotecan (Cpt-11)mentioning

confidence: 99%

Docetaxel: its role in current and future treatments for advanced gastric cancer

Nishiyama

Wada

2009

Gastric Cancer

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regimen are undetermined [1][2][3][4]. Both CF (cisplatin [CDDP]/5-fl uorouracil ) and ECF (epirubicin/ CDDP/5-FU) have been considered as reference regimens to date [5][6][7][8], but the median survival time (MST) of the regimens does not exceed 7-10 months.Recently, several active agents have been used in gastric cancer therapy: the taxanes, irinotecan (CPT-11), oxaliplatin, S-1, and capecitabine, and more recently, biological agents such as cetuximab and bevacizumab have been used [1][2][3][4][5][6][7][8]. Current studies have thus focused on "new-generation agents," and much effort has been directed towards the development of the best regimen in various treatment settings. A series of these trials have provided several regimens that could become a standard treatment: the regimens include docetaxel/CDDP/5-FU (DCF) and CDDP/S-1 for advanced and metastatic cancer, and S-1 monotherapy in the adjuvant setting [9][10][11]. The advent of these newgeneration agents offers hope for improving patient outcomes.Among the new-generation agents, docetaxel now appears to be one of the most extensively investigated [12]. Docetaxel has demonstrated promising activity in gastric cancer, both as monotherapy [13,14] and in combination with other agents [15][16][17]. To date, docetaxel combinations, especially the DCF regimen, seem to be pivotal [9,10], and further, a taxane has been suggested to be the best potential partner of new oral 5-FU analogues and prodrugs such as S-1 and capecitabine [16,17]. This review will focus on the taxane, docetaxel, as a key agent in gastric cancer chemotherapy. Docetaxel as a single agent Mechanisms of action and metabolismDocetaxel is a semisynthetic analogue of paclitaxel, an extract from the rare Pacifi c yew tree Taxus brevifolia [18]. The chemical structure of docetaxel differs from

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Section: Combinations With Irinotecan (Cpt-11)mentioning

confidence: 99%

Docetaxel: its role in current and future treatments for advanced gastric cancer

Nishiyama

Wada

2009

Gastric Cancer

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“…With these combinations time-to-progression (TTP) ranged between 5.5 and 8.0 months with an overall survival (OS) between 9.5 and 16 months. Serious cetuximab-related adverse events observed in all clinical trials were infusion reactions, skin toxicity, and diarrhea (Lordick et al 2007;Han et al 2009;Pinto et al 2008;Pinto et al 2007). Currently, there are phase III trials ongoing evaluating cetuximab in combination with various chemotherapy backbones (Tables 1, 2, 3).…”

Section: Egfr Inhibitorsmentioning

confidence: 95%

Gastric cancer in the era of molecularly targeted agents: current drug development strategies

Arkenau

2009

J Cancer Res Clin Oncol

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Gastric cancer is the second most common cause of cancer death worldwide with approximately one million cases diagnosed annually. Despite considerable improvements in surgical techniques, innovations in clinical diagnostics and the development of new chemotherapy regimens, the clinical outcome for patients with advanced gastric cancer and cancer of the GEJ is generally poor with 5-year survival rates ranging between 5 and 15%. The understanding of cancer relevant events has resulted in new therapeutic strategies, particularly in developing of new molecular targeted agents. These agents have the ability to target a variety of cancer relevant receptors and downstream pathways including the epidermal growth factor receptor (EGFR), the vascular endothelial growth factor receptor (VEGFR), the insulin-like growth factor receptor (IGFR), the c-Met pathway, cell-cycle pathways, and down-stream signalling pathways such as the Akt-PI3k-mTOR pathway. In the era of new molecularly targeted agents this review focuses on recent developments of targeting relevant pathways involved in gastric cancer and cancer of the GEJ.

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“…Cetuximab has been investigated in combination with oxaliplatin or docetaxel containing chemotherapy protocols [5][6][7][8]. In the fi rst line setting remission rates of 41-50% could be achieved.…”

Section: Biologicalsmentioning

confidence: 99%

“…In the fi rst line setting remission rates of 41-50% could be achieved. Toxicity was manageable although some trials reported higher gastrointestinal toxicity [6,8]. Han and co-authors [5] investigated KRAS mutation status and found that all patients expressed wild-type KRAS.…”

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confidence: 99%

Gastric cancer

Wöll¹

2008

memo

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Overall survival of patients suff ering from gastric cancer is still poor. Two-thirds of patients are diagnosed in a locally advanced stage or with metastatic tumour. But even in patients with operable disease recurrence rate is high. To increase the prognosis of this devastating disease much eff ort has been put in the development of curative and palliative therapy concepts recently. Th e aim of this article is to summarize the most important publications at this year's ASCO meeting and to put them into context of current therapeutic strategies. Palliative chemotherapyAn Asian phase III trial investigated the eff ect of the oral 5FU prodrug S1 in combination with 5FU compared to S1 and cisplatin or S1 monotherapy [1]. Th e combination S1 and cisplatin was superior to 5FU/S1 or S1 monotherapy as far as response rate and overall survival are concerned. Th e authors conclude that this will be the new Chinese standard. Given the substantial diff erences of S1 pharmacokinetics and because of the high interethnic variability [2] it remains to be shown whether this substance proves its effi cacy in a Caucasian population. Th e large international FLAGS trial investigating this issue in a western population will help to answer this question.A second phase III trial in inoperable gastric cancer patients compared docetaxel/cisplatin versus 5FU/cisplatin [3]. Both combinations showed comparable response rates and comparable overall survival of 9.4 and 10.2 months, respectively. Th e only diff erence could be shown in toxicity. Docetaxel/cisplatin showed more haematotoxicity whereas 5FU/cisplatin showed more gastrointestinal side eff ects.An interim analysis of a large (n = 3106, 17 randomized trials) individual patient data-based meta-analysis elucidated the benefi t of FU derivatives, anthracyclines, platinum salts, taxanes or irinotecan in the palliative setting [4]. Only the taxane-based regimens showed an overall survival benefi t compared with all other combinations but this result is mainly based on two trials. Th erefore fi nal analysis of this meta-analysis has to be awaited until conclusions can be drawn.Many phase II trials investigated diff erent chemotherapy doublets or triplets (Tab. 1). Th ese data support the role of taxanes, capecitabin, oxaliplatin as well as 5FU and cisplatin as active substances in the treatment of gastric cancer. Two phase II trials investigated sequential therapy strategies showing comparable effi cacy but lower toxicity (Tab. 2) making this approach interesting for the generation of future trials.Even in second and third line therapies phase II trials showed effi cacy (Tab. 3). In this partially heavily pre-treated cohort remission rates between 18% and 34% could be achieved with overall survival from 5 to 15 months. Although phase III trials in this setting are most likely unrealistic these phase II data among earlier trials favour second or even third line chemotherapy in selected patients. BiologicalsOnly phase II data are available as far as targeted therapies are concerned. Cetux...

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Cetuximab in combination with cisplatin and docetaxel as first-line treatment in patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Italian phase II DOCETUX study)

Cited by 13 publications

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Docetaxel: its role in current and future treatments for advanced gastric cancer

Docetaxel: its role in current and future treatments for advanced gastric cancer

Gastric cancer in the era of molecularly targeted agents: current drug development strategies

Gastric cancer

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