Intravenous Infusion Of Gemcitabine Research Articles

Ultrasound- and microbubble-enhanced chemotherapy for treating pancreatic cancer: A phase I clinical trial

Experimental research of ultrasound to induce or improve delivery has snowballed in the past decade. In our work, we investigate the use of low-intensity ultrasound in combination with clinically approved microbubbles to enhance the therapeutic efficacy of chemotherapy. Ten voluntary patients with locally advanced or metastatic pancreatic adenocarcinoma were consecutively recruited. Following standard chemotherapy protocol (intravenous infusion of gemcitabine over 30 min), a clinical ultrasound scanner was targeted at the largest slice of the tumour using modified non-linear contrast imaging settings (1.9 MHz center frequency, 0.27 MPa peak-negative pressure), and SonoVue® was injected intravenously. Ultrasound and microbubble treatment duration was 31.5 min. The combined therapy did not induce any additional toxicity or increase side effect frequency when compared to chemotherapy alone. Combination treated patients were able to tolerate an increased amount treatment cycles when compare historical controls (n = 63); average of 8.3±6.0 cycles, versus 13.8±5.6 cycles. The median survival also increased from 7.0 months to 17.6 months (p = 0.0044). In addition, five patients showed a primary tumor diameter decrease. Combined treatment of ultrasound, microbubbles, and gemcitabine does not increase side effects and may have the potential to increase the therapeutic efficacy of chemotherapy in patients with pancreatic adenocarcinoma.

Neoadjuvant gemcitabine-based accelerated hyperfractionation chemoradiotherapy for patients with borderline resectable pancreatic adenocarcinoma.

We report the response to pre-operative gemcitabine-based chemoradiotherapy for pancreatic adenocarcinoma. Thirty-five consecutive patients with borderline resectable pancreatic adenocarcinoma of UICC Stage II or III with portal vein invasion or tumor abutment of artery received radiotherapy (twice daily fractions of 1.5 Gy, 5 days/week, total dose: 36 Gy; 30 Gy for Phase I Level 1) with weekly intravenous infusions of gemcitabine (400, 600 and 800 mg/m(2)) at Days 1 and 8 for Phase I and 800 mg/m(2) for Phase II. Restaging was repeated after completion of chemoradiotherapy. Twenty-six of the 35 (74.3%) patients underwent resection. The dose-limiting toxicities were Grade 4 neutropenia and thrombocytopenia. The recommended regimen was total radiation dose of 36 Gy with gemcitabine 800 mg/m(2). Surgical resection was conducted in 11 of the 15 (73.3%) patients in Phase I study and 15 of the 20 (75.0%) in Phase II. After recommended dose chemoradiotherapy and surgical resection, the median disease-free survival was 17.4 months (5-year survival rate = 14.3%). The median overall survival time and 5-year survival rate were 41.2 months and 28.6%, respectively, for the 21 patients who underwent resection and 10.0 months and 0%, respectively, for those 5 who did not (P = 0.004). Our pre-operative gemcitabine-based chemoradiotherapy was well tolerated and safe.

A Case of Residual Non-Small Cell Lung Cancer Cells Coexisting With Newly Developed Small Cell Lung Cancer Cells in Ascitic Fluid after Chemotherapy for Non-Small Cell Lung Cancer

Sang Hyuk Park, M.D., Hyun-Sook Chi, M.D., Young Jin Kim, M.D., Young-Uk Cho, M.D., Seongsoo Jang, M.D., Chan-Jeoung Park, M.D., and Sang-We Kim, M.D.. Ann Lab Med 2014;34:163-5. https://doi.org/10.3343/alm.2014.34.2.163

Preoperative chemoradiotherapy, surgery and adjuvant therapy for resectable pancreatic cancer.

In order to improve the poor prognosis of pancreatic cancer, a combination therapy consisting of preoperative chemoradiotherapy, surgery and postoperative chemotherapy may be an ideal strategy; nevertheless, the influence of preoperative therapy to postoperative therapy is not investigated. Thirty patients with resectable pancreatic ductal adenocarcinoma were enrolled. A 40Gy of radiation (2Gy/day x 20 fractions/4 weeks) was administered together with intravenous infusion of gemcitabine (800mg/m2, days 1, 8 and 15) before surgery. Surgery was performed 3-7 weeks after the final fraction of radiation, and postoperative chemotherapy consisting of 1000mg/m2 gemcitabine (days 1, 8 and 15 every 4 weeks for 6 cycles) was started within 8 weeks after surgery. All 30 patients successfully completed preoperative therapy. Re-staging after such therapy showed radiologically unresectable disease in 4 patients and 1 patient rejected surgery. Among the 25 patients who underwent laparotomy, 21 underwent curative resection. After curative resection, 4 were inadequate in performance status, thus postoperative therapy could not be started. Ten patients completed postoperative adjuvant therapy. The combination therapy for resectable pancreatic cancer seems a feasible and effective approach, though preoperative therapy may reduce the feasibility of postoperative therapy.

The current situation of Sunitinib in treating non-small cell lung cancer

Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor, which are being used in clinic. It can inhibit more than 80 kinds of receptor’s tyrosine kinase, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors, vascular endothelial growth factor receptors (VEGFR), etc. And tyrosine kinase inhibitor is involved in connection with the generation and progression of many kinds of cancer including lung cancer. Several studies have evaluated the effect of Sunitinib on non-small cell lung cancer (NSCLC), by single agent, continuous daily dosing or in combination with chemotherapeutics (with docetaxel or gemcitabine plus cisplatin), which all showed certain effect. The test of Sunitinib in combination with gemcitabine plus cisplatin for advanced NSCLC shown that at the maximum tolerated dose: oral Sunitinib 37.5 mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) schedule with intravenous infusions of gemcitabine (1000 mg/m2 days 1, 8) and cisplatin (80 mg/m2 day 1), administered in 3-week cycles, 66.7% patients achieved partial responses. And adverse effects were mild to moderate in severity (grades 1 to 2). Therapy was generally well tolerated. In summary, all the evidence above suggests that Sunitinib may play an important role in the treating of NSCLC.

Sunitinib in combination with gemcitabine plus cisplatin for advanced non-small cell lung cancer: A phase I dose-escalation study

Purpose To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated. Methods Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50 mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25 mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250 mg/m 2 days 1, 8) and cisplatin (80 mg/m 2 day 1). Results A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22%) on Schedule 2/1 and 1 of 6 patients (17%) on the CDD schedule had confirmed partial responses. Conclusions The MTD was identified as sunitinib 37.5 mg (Schedule 2/1), gemcitabine 1250 mg/m 2, and cisplatin 80 mg/m 2, with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.

A phase II study of induction chemotherapy with gemcitabine plus S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer

The aim of this study was to investigate the feasibility and efficacy of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer. Patients with locally advanced unresectable pancreatic cancer received four cycles of induction chemotherapy consisting of 30-min intravenous infusions of gemcitabine 1,000 mg/m(2) on days 1 and 8 and oral S-1 40 mg/m(2) twice daily on days 1-14 of a 21-day cycle. Those without disease progression received chemoradiotherapy of 30 Gy in ten fractions with 250 mg/m(2) of gemcitabine on days 1 and 8. A total of 20 patients were treated. Median follow-up time was 431 days (range 133-1,014 days). Four cycles of induction chemotherapy were completed in 18 patients, and 16 patients received chemoradiotherapy, which was completed without delay in all. Grade 3-4 toxicities associated with induction chemotherapy were neutropenia (50%); anemia (20%); thrombocytopenia (10%); febrile neutropenia (5%); nausea (10%); anorexia (10%); and vomiting, fatigue, dehydration, stomatitis, and rash (5%). Grade 3-4 toxicities among those receiving chemoradiotherapy were neutropenia (13%) and anemia (6%). Median progression-free survival was 8.1 months. Median overall survival was 14.4 months, with a 1-year survival rate of 54.2%. The regimen of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy used in the present study demonstrated promising activity in locally advanced pancreatic cancer. Further consideration of radiation schedule and duration of induction chemotherapy is required to enhance the efficacy of this strategy.

Adjuvant Interferon-based Chemoradiation Followed By Gemcitabine for Resected Pancreatic Adenocarcinoma: A Single-Institution Phase II Study

This is a phase II, single-center, single-arm study of patients with resectable adenocarcinoma of the pancreas who were treated with adjuvant interferon-based chemoradiation followed by gemcitabine. The primary end point was 2-year overall survival, with secondary endpoints being 2-year disease-free survival, and the frequency of grade 3 or 4 toxicity. From April 2002 to September 2005, 53 patients with adenocarcinoma of the pancreas underwent curative resection at a single institution, and subsequently received interferon- and gemcitabine-based adjuvant therapy consisting of external-beam irradiation at a dose of 5040 cGy (25 fractions per 5 weeks) and simultaneous 3-drug chemotherapy consisting of (1) continuous infusion 5-fluorouracil (175 mg/m2); (2) weekly intravenous bolus cisplatin (25 mg/m2); and (3) interferon-alpha (3 million units subcutaneously 3 times per week) during the 6 weeks of radiation. This was followed by two 4-week courses of weekly intravenous infusion of gemcitabine (1000 mg/m2, 3 of 4 weeks). Median follow-up is 38 months. Seventy-seven percent of patients had node-positive disease. Sixteen patients (30%) failed to complete adjuvant therapy, due to disease progression (7 patients), toxicity (7 patients), and consent withdrawal (2 patients). No patients completed planned therapy without dose modification. Median overall survival was 25 months (confidence interval [CI] = 21.5-48.5 months). Actuarial overall survival for the 1-, 2- and 3-year periods were 75% (CI = 61-85%), 56% (CI = 41-69%), and 41% (26-55%), respectively. This phase II trial demonstrated increased patient survival compared with historical controls, and equivalent survival compared with the regimen combining interferon-alpha with 5-fluorouracil-based chemoradiation. Despite these encouraging results, significant concerns regarding dose- and treatment-limiting toxicities remain.

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.