Hiroshi Kojima

Phase II trial of paclitaxel and cisplatin as neoadjuvant chemotherapy for locally advanced gastric cancer

PurposePaclitaxel–cisplatin (TC) combination is effective and well tolerated in patients with unresectable gastric cancer. We investigated the efficacy and safety of TC for locally advanced gastric cancers in a neoadjuvant setting.MethodsPatients received 2–4 courses of paclitaxel (80xa0mg/m2) and cisplatin (25xa0mg/m2) on days 1, 8, and 15 in a 4-weekly schedule, followed by radical gastrectomy. Primary endpoint was the pathological response rate: percentage of tumors in which one-third or more parts were affected.ResultsAll 52 patients enrolled were eligible. Thirty-six (69.7xa0%) patients completed two or more courses of chemotherapy. Forty-three patients (82.7xa0%) underwent surgery, 33 (63.5xa0%) had R0 resection, and there was no treatment-related death. The pathological response was 34.6xa0% (95xa0% CI 22.0–49.1) for all registered patients; the null hypothesis of tumor response ≤10xa0% was rejected (pxa0<xa00.0001). The 3-year overall survival was 41.5xa0% (95xa0% CI 27.4–55.0).ConclusionsThe neoadjuvant chemotherapy with TC was safe and effective for patients with locally advanced gastric cancer, and further study is needed to confirm the effectiveness of this regimen.

Long-term follow up of patients who were positive for peritoneal lavage cytology: final report from the CCOG0301 study

BackgroundIn gastric cancer patients who have positive results for peritoneal lavage cytology the disease is defined as CY1, and classified as stage IV, and this population has generally suffered a dismal outcome. For this population, we had conducted a phase II trial, with the 2-year survival rate as the primary endpoint, to test the strategy of D2 dissection followed by chemotherapy with single-agent S-1 (1xa0M tegafur–0.4xa0M gimestat–1xa0M otastat potassium). Forty-eight patients were enrolled, of whom 47 were found to have been eligible for analysis. The 2-year survival rate of 46xa0% exceeded our expectations.MethodsFurther follow up was conducted to confirm whether radical surgery could be recommended for the CY1 population.ResultsThe 5-year overall and relapse-free survival rates were 26 and 21xa0%, respectively.ConclusionsGastrectomy with curative intent could be considered for patients with CY1 disease provided they are scheduled to receive effective postoperative chemotherapy.

CPT-11 as a second-line treatment for patients with advanced/metastatic gastric cancer who failed S-1 (CCOG0702)

BackgroundIn Japan, CPT-11 is often used to treat unresectable gastric cancer in the second-line setting. However, evidence regarding benefit of second-line chemotherapy remains sparse, especially after failing S-1.MethodsA phase II study to evaluate the efficacy and safety of weekly administration of CPT-11 at a dose of 100xa0mg/m2 after failing a S-1-containing first-line treatment was planned with response rate as a primary end point. UGT1A1*6, *27, and *28 genotyping were performed in all cases, and those found to have either homozygous for *28, homozygous for *6, heterozygous for both *6 and *28, and heterozygous for *27 were rendered ineligible for the phase II trial.ResultsTwo patients of homozygous for *28, two patients of homozygous for *6, and one patient of heterozygous for *27 were found among 39 recruited patients. The median number of courses delivered was 3 courses. The overall response rate was 15.4xa0% and disease control rate was 65.4xa0%. The median time to treatment failure was 87.5xa0days and median overall survival was 268xa0days. Twenty-two (73xa0%) of 30 valuable patients experienced protocol-specified skip of treatment and 8 (30xa0%) of patients could continue treatment with dose reduction. ≥G3 neutropenia was found in 30xa0% and ≥G3 anorexia and diarrhea were found in 23 and 17xa0%, respectively.ConclusionWeekly CPT-11 at 100xa0mg/m2 showed moderate response among gastric cancer patients who were refractory to S-1, but the disease control rate seemed meaningful. Even after selection of patients by UGT1A1 polymorphism of *6, *27, and *28, severe toxic events could not be prevented completely.

Detection of elevated proteins in peritoneal dissemination of gastric cancer by analyzing mass spectra data of serum proteins.

BACKGROUNDnRecently, several authors reported on the Protein Chip approach to analyze serum. They used SELDI-TOF-MS (surface enhanced laser desorption/ionization-time of flight-mass spectrometry) to identify patients with cancers of various origins in a highly sensitive and specific manner. In the current study, a similar approach was employed to analyze the serum of patients with various stages of gastric cancer.nnnMETHODSnControl serum specimens from patients with gastritis (n = 19) and those with gastric cancer (Stage I: n = 6, Stage II or III: n = 6, Stage IV: n = 6, total: n = 18) were collected and analyzed by the Protein Chip biomarker system (Bio-Rad, Japan), a platform for SELDI-TOF-MS, and protein profiles were obtained and compared. The cation exchange chip (CM10) and the anion exchange chip (Q10) were used for processing before TOF-MS.nnnRESULTSnnine proteins were significantly over-expressed (P < 0.05, Student t-test) in patients with gastric cancer compared to patients with gastritis. Among them, four protein masses with 2929 m/z, 3293 m/z, 3371 m/z, and 4213 m/z were found to be differentially expressed solely in patients suffering from peritoneal dissemination. All peaks were processed on CM10 chips. Employing one data mining method, CART (classification and regression trees), gastric cancer patients with peritoneal dissemination were successfully separated from those who had no peritoneal seeding.nnnCONCLUSIONnA validation study with a larger number of samples is mandatory; however, the detected peaks here might be candidates for biomarkers of peritoneal dissemination and/or gastric cancer. Moreover, further analysis of these four proteins might be helpful in revealing the mechanism of peritoneal dissemination, which at present has no cure.

Titration of serum CEA, p53 antibodies and CEA-IgM complexes in patients with colorectal cancer.

The early detection of colorectal cancer is key to the improvement of patient survival. Although fecal occult blood testing and carcinoembryonic antigen (CEA) in serum are widely used as non-invasive screening methods, they have limited sensitivity. Forty-five patients who underwent surgery for primary colorectal cancer were enrolled in this study. Sixteen (36%) were determined to have Stage I tumors, 15 (33%) Stage II tumors and 14 (31%) Stage III tumors. Serum samples from a non-colorectal cancer group of 22 patients with no tumors were analyzed as a control. In each serum sample, CEA, p53 antibodies and CEA-IgM complexes were measured. The combination of these three tests had an overall sensitivity of 53% (24/45), and revealed 31% (5/16) of the tumors to be in Stage I, 53% (8/15) to be in Stage II and 79% (11/14) to be in Stage III, while the false positive rate was 18% (4/22). The combined use of these three tests in serum is potentially an effective screening method for the detection of colorectal cancer, at even the early stages of the disease.

Successful endoscopic stent placement as a bridge to surgery for colonic obstruction induced by bevacizumab-based chemotherapy

The use of a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer is known to be effective. However, whether the use of a SEMS as a BTS for obstruction induced by effective chemotherapy (CTx) is useful is unknown. We present the case of a 54-year-old female patient with colorectal cancer who underwent SEMS placement as a BTS for colorectal obstruction induced by bevacizumab-based CTx. The patient was diagnosed as having transverse colon cancer with multiple liver metastases invading the inferior vena cava. Bevacizumab-based CTx was started; however, although it was effective, colonic obstruction occurred at the primary site after 31xa0months. A SEMS was placed as a BTS, and surgical resection of the primary lesion was performed after cessation of bevacizumab. However, the liver metastases remained unresectable. CTx was restarted after surgery, and 48-month survival was achieved. This case shows that SEMS placement as a BTS for colorectal obstruction induced by a good response to bevacizumab-based CTx was safe and beneficial. With the development of CTx and molecular-targeted agents, the frequency of colorectal obstruction associated with effective CTx is expected to increase. SEMS placement as a BTS might be one of the treatment options.