The Gastrointestinal (GI) Oncology Division

Introduction

The Gastrointestinal (GI) Oncology Division currently focuses on chemotherapy with or without radiation therapy for the treatment of GI malignancies, including head and neck cancer (HNC). For these conditions, standard chemotherapy has been administered in many patients as routine management. Investigational approaches using endoscopic, biological, and molecular analyses were evaluated by the Division to predict their clinical outcomes.

Routine Activities

The Division staff consists of 9 medical oncologists and 11 residents. In 2008, 1760 inpatients (640 newly diagnosed) were treated at our Division. Among these patients, more than 50 entered into clinical trials. Chemotherapy on an outpatient basis for probable candidates was managed passively, and the average hospital stay of patients treated with chemotherapy or palliative therapy was short (i.e., approximately 20 days). Inter-Divisional meetings with the Surgical/Radiation Oncology Divisions are held regularly to direct treatment for each patient or to discuss treatment strategies.

Esophageal Cancer (EC)

Many JCOG trials have been conducted for investigational new drugs.
The Division has also conducted an industrial trial on weekly paclitaxel for metastatic diseases and the results have been reported in the 2009 ASCO-GI meeting. Since 2005, more than 170 patients (stage II/III) have been treated definitively with the RTOG regimen as part of CRT (5-FU + CDDP + RT with 50.4 Gy (multiport irradiation)) along with passive surgical or endoscopic salvage procedures (EMR or photodynamic therapy) for treating residual/recurrent cancer after CRT. Based on these practical results, further clinical trials are presently being planned. To surrogate/predict the clinical benefits of definitive CRT, we are now prospectively attempting to profile the gene expression of biopsy specimens before therapy.

Gastric Cancer (GC)

Currently, the S-1 + cisplatin (CDDP) regimen is a standard first-line chemotherapy for advanced GC patients based on the results of two studies (JCOG9912 and SPRITS). S-1 monotherapy is a standard adjuvant chemotherapy for stage II/III GC patients based on the ACTS-GC result in Japan.
Several industrial- and investigator-initiated trials are presently ongoing. The enrollment of AVAGAST and ToGA was completed in late 2008. The results of JCOG 0106, which compares the efficacy of methotrexate + fluorouracil (5-FU) with that of 5-FU continuous infusion for GC patients with peritoneal metastasis will be reported in the 2009 ASCO annual meeting. A Phase I trial of sorafenib with S-1 + CDDP has been started. TYTAN, which evaluates the effectiveness of adding lapatinib to weekly paclitaxel as a second-line treatment for HER2-positive GC, is presently ongoing. A randomized phase II trial of irinotecan with/without nimotuzumab as second-line treatment has been stared. Based on the promising results of a phase II trial of everolimus, a phase III trial is being planned. Patient enrollment in JCOG 0407, which compares weekly paclitaxel with the best available 5-FU for GC with peritoneal metastasis, was also completed. A feasibility study of S-1 + cisplatin as adjuvant chemotherapy for stage III GC is presently ongoing following some protocol amendments.

Colorectal Cancer (CRC)

FOLFOX + bevacizumab (oxaliplatin + LV-modulated infusional 5-FU + bevacizumab) or FOLFIRI plus bevacizumab (irinotecan + LV-modulated infusional 5-FU + bevacizumab) has been routinely used in patients with metastatic or unresectable colorectal cancer. In 2008, more than 150 patients were successfully treated on an outpatient basis.
The global phase II trial of FOLFOX + sunitinib versus + bevacizumab, the phase I trial of FOLFIRI + bevacizumab (PK study) and the phase II trial of S-1 + bevacizumab as the first-line treatment, and the global phase II trial of standard chemotherapy + axitinib versus + bevacizumab, the phase I trial of irinotecan + TAS102 as the second-line treatment of colorectal cancer, are in progress.
In practice, adjuvant or neoadjuvant therapy has been carried out in cooperation with the Surgical Oncology Division. FOLFOX or 5-FU monotherapy has been routinely used as adjuvant therapy in patients who have undergone curative resection for stage III CRC. The evaluation of whether bevacizumab addition to chemotherapy as an adjuvant could reduce the risk of recurrence has already been completed.
Cetuximab, an anti-EGFR antibody, was approved for use in Japan in 2008. After the progression of bevacizumab-containing systemic chemotherapy, either cetuximab monotherapy or in combination with irinotecan was used for CRC patients with KRAS wild-type by direct sequencing. The phase II trial of panitumumab monotherapy has also been completed.

Head and Neck Cancer (HNC)

In 2008, more than 100 patients with locally advanced HNC received concurrent chemoradiotherapy and more than 40 patients with recurrent or metastatic HNC underwent chemotherapy in the Division. A multicenter phase II trial of chemoradiotherapy concurrent with S-1 and cisplatin in patients with unresectable locally advanced squamous cell carcinoma (JCOG 0706) is presently ongoing. A feasibility study of postoperative adjuvant chemoradiotherapy concurrent with high dose cisplatin for high risk HNC is also in progress. A phase I trial of chemotherapy combination with docetaxel, cisplatin and S-1 (TPS) for recurrent or advanced HNC has been completed, and the recommended TPS dose has been determined. Furthermore, we have participated in a global randomized phase III trial of chemotherapy with or without panitumumab for recurrent or metastatic HNC.

Others

Many early phase trials for GI-specific malignancies were conducted in 2008. A whole series of new drugs (1st administration in humans), including a PLK1 inhibitor, oral HSP inhibitors, and a WeeI inhibitor among others is likely to be introduced in 2008. Moreover, we will attempt to perform a DDI trial for FDA approval, and we are currently conducting several POC trials. All investigators of the GI Oncology Division have worked particularly hard to maintain our leadership in these new developments in Japan as well as on the global scale.

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