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- Byström, Per, et al.
(författare)
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Early prediction of response to first-line chemotherapy by sequential [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with advanced colorectal cancer
- 2009
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 20:6, s. 1057-1061
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To evaluate [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), for early evaluation of response to palliative chemotherapy and for prediction of long-term outcome, in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In a randomized trial, patients with mCRC received irinotecan-based combination chemotherapy. FDG-PET was carried out before treatment and after two cycles in 51 patients at two centers. Visual changes in tumor FDG uptake and changes measured semi-automatically, as standard uptake values (SUVs), were compared with radiological response after four and eight cycles. RESULTS: The mean baseline SUV for all tumor lesions per patient was higher in nonresponders than in responders (mean 7.4 versus 5.6, P = 0.02). There was a strong correlation between metabolic response (changes in SUV) and objective response (r = 0.57, P = 0.00001), with a sensitivity of 77% and a specificity of 76%. There was no significant correlation between metabolic response and time to progression (P = 0.5) or overall survival (P = 0.1). CONCLUSIONS: Although metabolic response assessed by FDG-PET reflects radiological tumor volume changes, the sensitivity and specificity are too low to support the routine use of PET in mCRC. Furthermore, PET failed to reflect long-term outcome and can, thus, not be used as surrogate end point for hard endpoint benefit.
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| 3. |
- Glimelius, Bengt, et al.
(författare)
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A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer
- 2010
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 21:5, s. 1020-1026
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Preclinically, protein kinase C and AKT activation can be inhibited by enzastaurin and reduce tumor growth of colorectal cancer cells. In asymptomatic patients with metastatic colorectal cancer (mCRC), enzastaurin activity was evaluated by measuring the 6-month progression-free survival (PFS) rate in a window study design. PATIENTS AND METHODS: Chemonaive patients with asymptomatic mCRC who did not require immediate chemotherapy-induced tumor reduction received a 400-mg thrice daily loading dose of enzastaurin on day 1 of cycle 1, followed by 500 mg once daily for the remaining 28-day cycles. Progression was assessed on the basis of radiographic imaging, rise in carcinoembryonic antigen or lactate dehydrogenase (LDH) levels or by appearance of clinical symptoms. RESULTS: Twenty-eight patients received daily enzastaurin. The 6-month PFS rate was 28% [95% confidence interval (CI) 13%-45%] and median PFS was 1.9 months (95% CI 1.8-4.5 months). Twelve (43%) patients had stable disease with a median duration of 6.1 months. The survival rate at 20 months was 77% (95% CI 47%-92%). No grade 4 toxicity was reported and grade 3 toxic effects were observed in three patients with one patient showing probable drug-related elevation of liver transaminases. CONCLUSION: The window design in asymptomatic patients with mCRC can be safely applied to assess the activity and safety of novel cytostatic agents like enzastaurin.
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| 6. |
- Ullenhag, G, et al.
(författare)
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Incidence of GM-CSF antibodies in cancer patients receiving GM-CSF for immunostimulation.
- 2001
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 99, s. 65-
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Tidskriftsartikel (refereegranskat)abstract
- We have assessed the immunogenicity profile of GM-CSF in patients with either colorectal carcinoma (CRC) at different stages of disease or with multiple myeloma who were given recombinant human GM-CSF (Escherichia coli-derived) combination therapy. Metastatic CRC patients received a colon carcinoma-reactive antibody and high doses of GM-CSF (425--500 microg/day for 10 days), while other CRC patients and those with myeloma received low doses of GM-CSF (75--80 microg/day for 4 days) as an adjuvant along with appropriate tumor antigens. We found that 55% of the patients (11/20) given high doses of GM-CSF developed GM-CSF-reactive antibodies in comparison with an incidence of only 16% (4/25) in patients given low doses of GM-CSF. None of the patients developed neutralizing antibodies and so the biological effects of GM-CSF were not compromised. A majority of patients (80%) (36/45) also developed antibodies to E. coli proteins that were present as trace contaminants in the GM-CSF product. Treatment with recombinant GM-CSF products, therefore, may induce antibodies against this cytokine depending on the regimen and the amounts used. In this study, multiple immunizations with low doses of GM-CSF was associated with a low incidence of GM-CSF antibodies, which did not neutralize the effect of the cytokine. This therapeutic strategy was effective in inducing adjuvant-type effects and needs to be explored in further clinical trials with this cytokine.
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