The Gastrointestinal (GI) Oncology Division

Introduction

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

Routine Activities

The staff of the Division consists of 9 medical oncologists and 8 residents. In 2007, 1760 inpatients (640 of whom had been newly diagnosed) were treated at our division. Among these patients, >50 were 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 routinely to direct treatment for each patient or to discuss treatment strategies.

JCOG trials for esophageal　cancer
Stage Phase Treatment JCOG
I II Combination of EMR &CRT 0508
  III Randomizing surgery vs. CRT 0502
II/II I/II S-1 + CDDP +RT 0604
TA/IV III Standard-dose vs.   Low-dose 0303
    CRT  
  I/II DCF Planne d

Esophageal Cancer (EC)

For investigational new drugs, many JCOG trials have been conducted.
The Division has also conducted an industrial trial on weekly paclitaxel for metastatic diseases. Since 2005, >150 patients (in stage II/III) have been treated definitively with the RTOG regimen as a 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 now are prospectively challenge to profile the gene-expression of biopsy specimens before therapy.

Gastric Cancer (GC)

Two Japanese phase III trials (JCOG9912&SPRITS) have met the primary endpoint in terms of overall survival. . Based on the promising results of these 2 studies, the S-1 + CDDP regimen is administered in Japanese patients as a standard therapy for advanced/metastatic GC. Several industrial phase II/III trials for evaluating first- and second-line therapy of GC with new active agents (trastuzumab, bevacizumab, lapatinib, lapatinib, everolimus, etc.) are also either in progress or are being planned. Extensive earlier phase clinical trials for POC have been conducted with particular focus on the development of molecular targeting drugs. For patients having GC with peritoneal dissemination, a randomized phase II trial (JCOG0407) of second-line chemotherapy (weekly paclitaxel vs. best available 5-FU) is in the enrollment stage. Progress has also been made in the field of adjuvant chemotherapy (AC). An interim analysis revealed a significant survival benefit of AC with S-1 for GC patients. Therefore, S-1 is used as a standard adjuvant chemotherapeutic agent for stage II/III GC patients. At present, a feasibility study of S-1 + CDDP for stage III GC patients is in progress as a preparation for a future phase III trial.

Colorectal Cancer (CRC)

FOLFOX plus 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 2007, >150 patients were successfully treated on an outpatient basis.
The phase I/II trial of FOLFOX + sunitinib and that of FOLFIRI + bevacizumab (PK study) and the phase II trial of S-1 + bevacizumab as the first-line treatment of colorectal cancer are in progress. The Division has also participated in a global phase III trial of FOLFIRI with or without panitumumab as the second-line treatment of colorectal cancer.
In practice, adjuvant or　neoadjuvant therapy has　been carried out with the cooperation of 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 colorectal cancer. It was completed to evaluate whether the addition of bevacizumab to chemotherapy as an adjuvant could reduce the risk of recurrence.
Cetuximab, an anti-EGFR antibody, will be approved for use in Japan in late 2008. The phase II trial of panitumumab monotherapy has already been completed. The efficacy and safety of the above novel agents were consistent with the results that have been previously reported in the Western countries.

Head and Neck Cancer (HNC)

In 2007, >80 patients with locally advanced HNC were treated with concurrent chemoradiotherapy, and >30 patients with recurrent or metastatic HNC were also treated with chemotherapy in this Division. Patient accrual for a multicenter phase II trial of concurrent CRT with S-1 and CDDP for locally advanced unresectable HNC (JCOG0706) will commence in 2008. An investigator-driven phase I trial of induction chemotherapy with docetaxel, cisplatin, and S-1 (TPS) for locally advanced HNC is in progress.

Others

Many early phase trials for GI-specific malignancies were conducted in 2007. A whole series of new drugs, including IGF-RI, HSP inhibitors, WII inhibitors, etc., is likely to be introduced in 2008. Investigators in the GI Oncology Division have worked particularly hard to maintain their leadership in these new developments in Japan as well as on the global scale.

● T. Doi ●

Number of patients in the GI Oncology
  2007
Total number of inpatients 1760
No. of new referrals 640
Endoscopic treatment 356
Chemotherapy cases 619
Esophageal cancer 169
Stomach cancer 151
Colorectal cancer 192
H & N cancer 118

Clinical studies (IND)
Organ affected by cancer Regimen Phase No
Stomach Capecitabine + CDDP ± Herceptin III 6
Capecitabine + CDDP ± Avastin II 4
RAD001 II 4
Weekly PTX ±Lapatinib III 1
S-1 + L-OHP I/II 5
Colorecta Panitumumab ±FOLFIRI III 5
SU11248 ±FOLFOX II 0
S1＋Avastin II 0
Adjuvant AVANT (XELOX or FOLFOX ± Avastin) III 3
H & N/EC S1 + CDDP + RT (JCOG0706) AMG655 I/II 4
NON TAS102, NK012, I 2
MK2461，AMG655
TAK285,VEGF-TRAP		   1

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