Phase I Trial Evaluating the Safety of Bevacizumab With Concurrent Radiotherapy and Capecitabine in Locally Advanced Pancreatic Cancer

Crane, Christopher H.; Ellis, Lee M.; Abbruzzese, James L.; Amos, Christina; Xiong, Henry Q.; Ho, Linus; Evans, Douglas B.; Tamm, Eric P.; Ng, Chaan S.; Pisters, Peter W.T.; Charnsangavej, Chusilp; Delclos, Marc E.; O’Reilly, Michael S.; Lee, Jeffrey E.; Wolff, Robert A.

doi:10.1200/jco.2005.03.6780

Cited by 195 publications

(108 citation statements)

References 21 publications

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“…Moreover, novel innovative CRT regimens for LAPC including newer agents (e.g. oral fluoropyrimidines and biologicals) are currently under investigation in phase I and II clinical trials (Crane et al, 2006;Duffy et al, 2008;Kim et al, 2009;Michael et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer – a multi-centre randomised phase II study

et al. 2009

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BACKGROUND: No standard treatment for locally advanced pancreatic cancer (LAPC) is defined. PATIENTS AND METHODS: Within a multi-centre, randomised phase II trial, 95 patients with LAPC were assigned to three different chemoradiotherapy (CRT) regimens: patients received conventionally fractionated radiotherapy of 50 Gy and were randomised to concurrent 5-fluorouracil (350 mg m À2 per day on each day of radiotherapy, RT-5-FU arm), concurrent gemcitabine (300 mg m À2 ), and cisplatin (30 mg m À2 ) on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by sequential full-dose gemcitabine (1000 mg m À2 ) and cisplatin (50 mg m À2 ) every 2 weeks (RT-GC þ GC arm). Primary end point was the overall survival (OS) rate after 9 months. RESULTS: The 9-month OS rate was 58% in the RT-5-FU arm, 52% in the RT-GC arm, and 45% in the RT-GC þ GC arm. Corresponding median survival times were 9.6, 9.3, and 7.3 months (P ¼ 0.61) respectively. The intent-to-treat response rate was 19, 22, and 13% respectively. Median progression-free survival was estimated with 4.0, 5.6, and 6.0 months (P ¼ 0.21). Grade 3/4 haematological toxicities were more frequent in the two GC-containing arms, no grade 3/4 febrile neutropaenia was observed. CONCLUSION: None of the three CRT regimens tested met the investigators' definition for efficacy; the median OS was similar to those previously reported with gemcitabine alone in LAPC.

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Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer – a multi-centre randomised phase II study

et al. 2009

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“…However, as recently shown in rectal cancer, targeted therapies may play a role as radiosensitizers (22). A recent phase I dose-escalation study in patients with locally advanced pancreatic cancer evaluated the toxicity of capecitabine and bevacizumab combined with radiotherapy (23). Acute toxicity was minimal and easily managed by reducing the dose of capecitabine without interruption or attenuation of either bevacizumab or radiation dose.…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy

Casneuf

Demetter²,

Boterberg³

et al. 2009

Oncol Rep

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Abstract. This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P<0.001, P<0.01 and P<0.05 compared to placebo). MVD was lowest in RT/SUN treated mice [compared to placebo (P<0.05), GEM (P<0.05) and GEM/SUN (P<0.01)]. Highest VEGF levels were seen after RT and RT/SUN treatment [vs. placebo (P<0.001) and vs. other treatments (P<0.01 for all comparisons)]. GEM and SUN in monotherapy lead to an up-regulation of PlGF and EGF, respectively. In conclusion, the combination treatments RT/SUN and GEM/SUN result in a more potent antiangiogenic and antitumor effect when compared to either treatment alone. Multitargeted angiogenesis inhibitor therapy with sunitinib combined with either radiotherapy or gemcitabine may be a novel approach for human pancreatic cancer.

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“…4,5 For patients with locally advanced disease, randomized trials have demonstrated improvement in median survival with chemoradiation compared with either chemotherapy or radiation therapy alone. 6,7 In a disease with such a dismal prognosis, symptom management and quality of life are paramount considerations. Patients with pancreatic cancer usually present with symptoms such as weight loss, fatigue, and pain.…”

Section: Introductionmentioning

confidence: 99%

Patterns of Self-Reported Symptoms in Pancreatic Cancer Patients Receiving Chemoradiation

Reyes‐Gibby

Chan

Abbruzzese

et al. 2007

Journal of Pain and Symptom Management

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Pancreatic cancer is a lethal disease characterized by multiple disease-related symptoms. Chemoradiation therapy is a standard of treatment for locally advanced pancreatic cancer. Although shown to prolong survival, there is little information about treatment-related symptoms or the palliative benefits of chemoradiation. We assessed symptoms of patients with locally advanced pancreatic cancer receiving chemoradiation to determine the prevalence, and co-occurrence, of symptoms and to identify the extent to which symptoms interfered with function. Forty-eight patients were treated with chemoradiation on a Phase I protocol. Patients received radiotherapy (50.4 Gy in 28 fractions), capecitabine (median dose 825 mg/m 2 twice daily), and bevacizumab (2.5-10 mg/kg). Symptom severity and its interference with function were prospectively assessed (at presentation, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript during, and after chemoradiation) in 43 consenting patients using the M.D. Anderson Symptom Inventory. Results showed that 95% of patients reported at least one of the 13 symptoms assessed at presentation. The most commonly reported symptoms of moderate to severe (≥5 on a 0-10 scale) intensity at presentation were lack of appetite (24%), pain (19%), fatigue (19%), and sleep disturbance (10%). We observed an increase in patients reporting moderate to severe fatigue, nausea, and sleep disturbance during chemoradiation. McNemar tests for paired binary observations showed the proportion of patients reporting moderate to severe symptoms significantly (P < 0.001) decreased after chemoradiation at 94 days follow-up (lack of appetite = 7%, pain = 7%, fatigue = 13%, sleep disturbance = 7%). This study demonstrates the feasibility and usefulness of symptom assessment in chemoradiation protocols. Future studies with larger cohorts are needed to further characterize multiple symptoms associated with chemoradiation.

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Phase I Trial Evaluating the Safety of Bevacizumab With Concurrent Radiotherapy and Capecitabine in Locally Advanced Pancreatic Cancer

Cited by 195 publications

References 21 publications

Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer – a multi-centre randomised phase II study

Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer – a multi-centre randomised phase II study

Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy

Patterns of Self-Reported Symptoms in Pancreatic Cancer Patients Receiving Chemoradiation

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