First-Line Gemcitabine, Nab-Paclitaxel, and Oxaliplatin Chemotherapy With Itraconazole in Patients With Metastatic Pancreatic Cancer: A Single Institution Experience.

BACKGROUND/AIM: Combination chemotherapy with gemcitabine, nab-paclitaxel, oxaliplatin, and itraconazole (GnPO-ITC) was administered as first-line chemotherapy in patients with metastatic pancreatic cancer (mPC). The efficacy and toxicity of these treatments were retrospectively investigated. PATIENTS AND METHODS: A total of 81 patients (mean age=64 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 were enrolled in the study, and administered nab-paclitaxel (125 mg/m2), gemcitabine (1,000 mg/m2), and oxaliplatin (85 mg/m2) on day 1 and itraconazole (400 mg) on days -2 to +2, repeated every 2 weeks. RESULTS: Metastatic sites observed in patients included the liver (n=55, 68%), peritoneum (n=23, 28%), distant lymph nodes (n=24, 30%), and lungs (n=18, 22%). Within 28 days after initiation of chemotherapy, 15 patients (19%) experienced common ≥3 grade hematological adverse events. The major reason for discontinuation of treatment among the responders was peripheral sensory neuropathy in 36 patients (44%). The overall response rate to treatment was 64% [95% confidence interval (CI)=54-75%]. The median progression-free survival and median overall survival were 8.3 months (95% CI=6.8-9.8 months) and 14.4 months (95% CI=11.4-17.3 months), respectively. Among the 52 responders, 24 (46%) underwent conversion surgery, which did not improve survival (p=0.279). Second-line treatment with irinotecan was required in 71 (88%) patients. Hepatic arterial chemotherapy and radiotherapy were administered to 33 (41%) and 27 (33%) patients, respectively. CONCLUSION: The GnPO-ITC regimen showed promising efficacy with manageable toxicities for controlling disease progression and improving overall survival.

[A case of unresectable gastric cancer treated with triplet combination chemotherapy with itraconazole and conversion surgery].

A 73-year-old woman visited our hospital due to carcinoembryonic antigen (CEA) level elevation (110ng/ml). She underwent an upper gastrointestinal endoscopy (EGD), enhanced computed tomography (CT), and positron emission tomography (PET) -CT. She was diagnosed with type 3 esophagogastric junction cancer with paraaortic lymph node (LN) metastases at stage IVA (cT3N4M0). She underwent triplet combination chemotherapy with itraconazole (ITCZ):nab-paclitaxel, oxaliplatin, and S-1 with ITCZ. After six cycles of this regimen, the CEA level was within normal range, and EGD and PET-CT showed no evidence of malignancy. She underwent laparoscopic proximal gastrectomy and lower esophagectomy. The surgical specimen revealed no residual tumor (pathological complete response). Three months later, her CEA level increased to 60.5ng/ml, and she had longitudinal LN recurrence. However, she took S-1 orally for 11 cycles, and the recurrent metastatic LNs improved. She received chemotherapy, including nivolumab followed by ramucirumab and nab-paclitaxel with ITCZ. The CEA level returned to the normal range, and PET-CT showed no evidence of malignancy. Her progression has been stable for 45 months after diagnosis. In summary, we encountered a case of unresectable gastric cancer with conversion surgery after triplet combination chemotherapy with ITCZ.

S-1, Oxaliplatin, Nab-paclitaxel and Itraconazole for Conversion Surgery for Advanced or Recurrent Gastric Cancer.

AIM: To evaluate the efficacy of chemotherapy with itraconazole for advanced or recurrent gastric cancer. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2 (HER2) negative unresectable gastric cancer referred to our hospital were included. The regimen comprised 160 mg/m2 nab-paclitaxel i.v. and 100 mg/m2 oxaliplatin i.v. on day 1, 60 mg/m2 S-1 orally on days 1-3, and 400 mg itraconazole orally on days -2 to 2, repeated every 2 weeks for 6-8 cycles. RESULTS: Twenty-three patients aged 40-80 years (median age=68 years) were enrolled, of whom 21 had stomach cancer and two gastroesophageal junction cancer. Regarding stage, two, one, and 20 patients had stage IIIA, IIIB, and IV, respectively. Among patients with liver metastases, 2/10 had simultaneous lung metastases. Nine patients had peritoneal dissemination, and five patients with stage IV disease developed recurrence after primary surgery followed by adjuvant S-1. The other 18 patients had no history of surgery or chemotherapy. The response rate was 70% (complete response in two; partial response in 14). Among 12 patients (67%) who underwent conversion surgery, R0 resection was conducted in eight, and no residual tumour was observed in two. For the population overall, the median overall survival was 24 months (95% confidence intervaI=21 months-not reached) and the 1-year overall survival rate was 95% (95% confidence intervaI=67-98%). Grade 3/4 neutropenia and grade 2 peripheral sensory neuropathy occurred in five (22%) and six (26%) patients, respectively, while no patient developed grade 3/4 thrombocytopenia. CONCLUSION: Chemotherapy with itraconazole is promising for patients with unresectable gastric cancer.