Shin Kuwakado

Retrospective Study as First-Line Chemotherapy Combined Anti-VEGF Antibody with Fluoropyrimidine for Frail Patients with Unresectable or Metastatic Colorectal Cancer

Background/Aim: Combination chemotherapies of oxaliplatin or irinotecan with fluoropyrimidine and molecular target drug were reported to be active in several clinical studies and so regarded as a first-line standard therapy for unresectable or metastatic colorectal cancer. However, the incidence of adverse events is not so low. We investigated the efficacy and safety of chemotherapy combined bevacizumab with fluoropyrimidine as a first-line treatment for frail patients. Methods: Twenty-six patients with unresectable or metastatic colorectal cancer who were treated with first-line chemotherapy combined bevacizumab with S-1 or 5FU/LV (modified Roswell Park Memorial Institute regimen) at our hospital between October 2007 and December 2010 were retrospectively investigated. Results: The median age was 72 years (range 66–84). Performance status was 0, 1 and 2 in 8, 17 and 1 patient, respectively. The primary lesion was located in the colon in 14 patients and in the rectum in 12. Twenty patients were with resection of the primary lesion and 6 were without, 8 were with postoperative adjuvant chemotherapy and 18 were without. The number of metastasized organs was 1, 2 and 3 in 17, 9 and 0 patients, respectively. The liver, lung, lymph node and peritoneum were metastasized in 9, 9, 11 and 5 patients, respectively. The KRAS gene was wild in 11, mutated in 7 and unknown in 8 patients. Bevacizumab with S-1 was used in 17 patients and bevacizumab with 5FU/LV was used in 9. Response and disease control rates were 50 and 100%, respectively. The median duration of progression-free survival was 9.1 months and the median time to treatment failure was 9.0 months. The incidences of all grades of neutropenia and hypertension were 31%, those of grade 3 or severer were 12%, and those of other adverse events were low. Grade 3 cerebral hemorrhage, grade 4 pulmonary embolism and grade 5 febrile neutropenia each occurred in 1 patient. Conclusion: The first-line chemotherapy combined bevacizumab with fluoropyrimidine for frail patients with unresectable or metastatic colorectal cancer in Japan was comparable to the safety and efficacy of combination therapy reported previously in Western countries.

Efficacy of Prophylactic G-CSF in Patients Receiving FOLFIRINOX: A Preliminary Retrospective Study.

OBJECTIVE Recent guidelines have adopted an incidence of febrile neutropenia (FN) threshold of 20% for the use of prophylactic granulocyte colony-stimulating factor (G-CSF). In a Japanese phase II study of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) for Japanese patients with advanced pancreatic cancer, the incidence of FN and severe neutropenia were 24.7% and 77.8%, respectively, without G-CSF prophylaxis. The aim of this retrospective study was to investigate the incidence of FN or severe neutropenia induced by full-dose FOLFIRINOX administration with G-CSF prophylaxis during the first cycle of treatment. METHODS Patients with advanced pancreatic cancer who received FOLFIRINOX with G-CSF prophylaxis during the first cycle of treatment from January 2014 to August 2014 were investigated and the frequency of adverse events during the first cycle was measured. RESULTS Among seven patients who received FOLFIRINOX, six patients met the eligibility criteria. The patient characteristics were as follows: median age (range), 57 (50-66); men/women, 3/3; performance status 0/1, 2/4. Grade 3/4 hematological adverse events were as follows: leukopenia in 33% of the patients, neutropenia in 33% of the patients, thrombocytopenia in 33% of the patients and FN in 17% of the patients. One patient was heterozygous for the UGT1A1*6 and UGT1A1*28 polymorphisms and experienced FN. Grade3/4 non-hematological adverse events were as follows: anorexia in 33% of the cases and nausea in 50% of the cases. CONCLUSION Although the present study was retrospective and small, the simultaneous administration of G-CSF might be effective for the prevention of severe neutropenia and FN in patients treated with FOLFIRINOX.

Efficacy and feasibility of neoadjuvant chemotherapy and chemoradiotherapy for elderly patients with stage IB/II/III (excluding T4) esophageal cancer: Retrospective study.

135 Background: Neoadjuvant chemotherapy (NAC) of 5-fluorouracil plus cisplatin infusion (FP) is standard therapy for stage IB/II/III (excluding T4) esophageal cancer from results of JCOG9907 and definitive chemoradiotherapy (dCRT) of FP is one of the curative options for resectable esophageal cancer with organ preservation results of JCOG9906 in Japan. However, the efficacy and feasibility of NAC FP and CRT for elderly patients (pts) are unclear. Methods: We examined stage IB/II/III (excluding T4) esophageal cancer pts aged 70 or over, who received NAC FP or dCRT at our institution between April 2008 and August 2015, retrospectively. Results: 16 pts received NAC FP at least 1 course, while 5 pts received dCRT because of intolerability for surgery, reject of surgery, and patients wish. Median age was 73/75 (NAC FP/dCRT) and pts in NAC FP had more advanced stage cancer compared with pts in dCRT (p = 0.02). With respect to the toxicity, bone marrow depression developed in dCRT with more high frequency comp...

A phase II study of panitumumab plus irinotecan for metastatic colorectal cancer with wild KRAS, resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese (OGSG1001).

607 Background: Anti-epidermal growth factor receptor (EGFR) antibody therapy showed to be effective in treatment for metastatic colorectal cancer (mCRC) with wild KRAS. Especially, combination chemotherapy with anti-EGFR antibody plus irinotecan is expected more effective than anti-EGFR antibody alone, resistant to irinotecan. We conducted a phase II trial of panitumumab plus irinotecan for mCRC with wild KRAS resistant to fluoropyrimidine, oxaliplatin, and irinotecan in Japanese. Methods: Subjects were mCRC patients with wild KRAS, who showed resistance to fluoropyrimidine, oxaliplatin, and irinotecan and had measurable disease, ECOG PS 0-2. Panitumumab (6 mg/kg) plus irinotecan (same dose as prior irinotecan) was administered every two weeks. This treatment was provided until progression. The primary endpoint was response rate (RR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), response duration, and adverse event (AE). Results: A total of ...

1492PTHE IMPACT OF ADDING APREPITANT FOR THE PATIENTS RECEIVING MODERATE RISK OF EMETOGENIC CHEMOTHERAPY, A PROSPECTIVE, RANDOMIZED, CROSS-OVER TRIAL.

ABSTRACT Aim: Aprepitant, a neurokinin 1 antagonist, showed efficacy for chemotherapy-induced nausea and vomit(CINV). Antiemetic guidelines recommend aprepitant for high emetogenic chemotherapy(HEC). This prospective, randomized, cross-over trial aimed to evaluate the efficacy of aprepitant for patients(pts) receiving moderate emetogenic chemotherapy(MEC). Methods: Gastrointestinal cancer pts receiving MEC were randomly assinged to GroupA and B. We administered as follows; in GroupA; on first course, pts received palonosetron (0.75mg iv on day 1) and dexamethasone (9.9mg on day 1, and 8mg p.o. on days 2-3) (control premedication) and on second course, pts received oral aprepitant (125mg on day 1 and 80mg on days 2-3) with control premedication (dexamethasone; 4.95mg iv and 4mg p.o.). In GroupB, pts received aprepitant with control premedication on the first course and they received control premedication on second course. The primary endpoint was rate of CR (complete response; neither emesis nor rescue therapy) and degree of nausea. Results: From January 2011 to March 2013, 100 pts were enrolled, and 83 pts were analyzed(female/male, 35/48; median age, 65 years; colorectal/gastric, 64/19; irinotecan/oxaliplatin 53/30). The CR rates of aprepitant/control were 73.5%/60.2%(p = 0.064). The degree of nausea was(more than intermediate) was 4.9%/19.0%(p = 0.02). Conclusions: Adding aprepitant significantly reduced moderate and severe emesis compared with standard premedication. Although the rate of CR was not statistically significant, aprepitant reduced the degree of nausea. Adding aprepitant is promising for gastrointestinal cancer pts receivig MEC. Disclosure: All authors have declared no conflicts of interest.