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Berglund, Ake
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Publications (10 of 23) Show all publications
Whither, S. B., Liposits, G., Skuladottir, H., Hofsli, E., Shah, C.-H., Poulsen, L. Ö., . . . Pfeiffer, P. (2019). Reduced-dose combination chemotherapy (S-1 plus oxaliplatin) versus full- dose monotherapy (S-1) in older vulnerable patients with metastatic colorectal cancer (NORDIC9): a randomised, open-label phase 2 trial. The Lancet Gastroenterology & Hepatology, 4(5), 376-388
Open this publication in new window or tab >>Reduced-dose combination chemotherapy (S-1 plus oxaliplatin) versus full- dose monotherapy (S-1) in older vulnerable patients with metastatic colorectal cancer (NORDIC9): a randomised, open-label phase 2 trial
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2019 (English)In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 4, no 5, p. 376-388Article in journal (Refereed) Published
Abstract [en]

Background: Older or vulnerable patients with metastatic colorectal cancer are seldom included in randomised trials.The multicentre NORDIC9 trial evaluated reduced-dose combination chemotherapy compared with full-dose monotherapy in older, vulnerable patients.

Methods: This randomised, open-label phase 2 trial was done in 23 Nordic oncology clinics and included patients aged 70 years or older with previously untreated metastatic colorectal cancer who were not candidates for full-dose combination chemotherapy. Patients were block randomised (1: 1) using a web-based tool to full-dose S-1 (30 mg/m(2) orally twice daily on days 1-14 every 3 weeks) followed by second-line treatment at progression with irinotecan (250 mg/m(2) intravenously on day 1 every 3 weeks or 180 mg/m(2) intravenously on day 1 every 2 weeks) or reduceddose combination chemotherapy with S-1 (20 mg/m(2) orally twice daily on days 1-14) and oxaliplatin (100 mg/m(2) intravenously on day 1 every 3 weeks) followed by second-line treatment at progression with S-1 (20 mg/m(2) orally twice daily on days 1-14) and irinotecan (180 mg/m(2) intravenously on day 1 every 3 weeks). Use of bevacizumab (7.5 mg/kg intravenously on day 1 of each cycle) was optional. Treatment allocation was not masked and randomisation was stratified for institution and bevacizumab. The primary outcome was progression-free survival. Survival analyses were by intention to treat and safety analyses were done on the treated population. This trial is registered with EudraCT, number 2014-000394-39, and is closed to new participants.

Findings: From March 9, 2015, to Oct 11, 2017, 160 patients with a median age of 78 years (IQR 76-81) were randomly assigned to full-dose monotherapy (n=83) or reduced-dose combination chemotherapy (n=77). At data cutoff (Sept 1, 2018; median follow-up 23.8 months [IQR 18.8-30.9]), 81 (98%) patients in the full-dose monotherapy group and 71 (92%) patients in the reduced-dose combination group had progressed or died. Median progression-free survival was significantly longer with reduced-dose combination chemotherapy (6.2 months [95% CI 5.3-8.3]) than with full-dose monotherapy (5.3 months [4.1-6.8]; hazard ratio [HR] 0.72 [95% CI 0.52-0.99]; p=0.047). Toxicity was evaluated in 157 patients who received treatment. Significantly more patients in the full-dose monotherapy group (51 [62%] of 82 patients) experienced at least one grade 3-4 adverse event than in the reduced-dose combination group (32 [43%] of 75 patients; p=0.014). Grade 3-4 diarrhoea (12 [15%] vs two [3%]; p=0.018), fatigue (ten [12%] vs three [4%]; p=0.083), and dehydration (five [6%] vs none; p=0.060) were more frequent in the full-dose monotherapy group than in the reduced-dose combination group. Treatment-related deaths occurred in three patients during firstline treatment and three patients during second-line treatment (two in the full-dose monotherapy group vs one in the reduced-dose combination group in both cases).

Interpretation: Reduced-dose combination chemotherapy with S-1 and oxaliplatin for older, vulnerable patients with metastatic colorectal cancer was more effective and resulted in less toxicity than full-dose monotherapy with S-1. Reduced-dose combination chemotherapy could be a preferred treatment for this population.

Place, publisher, year, edition, pages
ELSEVIER INC, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-382373 (URN)10.1016/S2468-1253(19)30041-X (DOI)000463786300023 ()30852136 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-04-26Bibliographically approved
Erlandsson, J., Holm, T., Pettersson, D., Berglund, Å., Cedermark, B., Radu, C., . . . Martling, A. (2017). Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. The Lancet Oncology, 18(3), 336-346
Open this publication in new window or tab >>Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial
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2017 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, no 3, p. 336-346Article in journal (Refereed) Published
Abstract [en]

Background: Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery.

Methods: In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 x 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 x 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1.7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813.

Findings: Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33.4 months (range 18.2-62.2) in the short-course radiotherapy group and 19.3 months (8.5-39.5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33.3 months (range 17.8-114.3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1.44 [95% CI 0.41-5.11]; long-course radiotherapy with delay 2.24 [0.71-7.10]; p=0.48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (<1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0.59 [95% CI 0.36-0.97], long-course radiotherapy with delay 0.63 [0.38-1.04], p=0.075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0.61 [95% CI 0.45-0.83] p=0.001).

Interpretation: Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-318940 (URN)10.1016/S1470-2045(17)30086-4 (DOI)000396344600045 ()28190762 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyStockholm County Council
Available from: 2017-04-03 Created: 2017-04-03 Last updated: 2017-11-29Bibliographically approved
Winther, S. B., Österlund, P., Berglund, Å., Glimelius, B., Qvortrup, C., Sorbye, H. & Pfeiffer, P. (2017). Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer: NORDIC 9. BMC Cancer, 17, Article ID 548.
Open this publication in new window or tab >>Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer: NORDIC 9
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2017 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 548Article in journal (Refereed) Published
Abstract [en]

Background: Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available. Improved geriatric assessments are needed to select which older patients should receive therapy.

Methods: The NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m(2) twice daily days 1-14 every 3 weeks, followed by second line irinotecan 250-350 mg/m(2) iv day 1 every 3 weeks or 180-250 mg/m(2) iv day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m(2) days 1-14 + oxaliplatin 100 mg/m(2) iv day 1 every 3 weeks, followed by second line S-1 20 mg/m(2) days 1-14 + irinotecan 180 mg/m(2) day 1 every 3 week) for older patients (>= 70 years) with mCRC who are not candidates for full-dose standard combination therapy. Additional bevacizumab (7.5 mg/kg) is optional in first-line. Blood samples and tumor tissue will be collected to investigate predictive markers. Geriatric screening tools (G-8, VES-13, Timed-Up-and- Go and Handgrip strength), Charlson Comorbidty Index and quality of life (EORTC QLQ-C30) will be evaluated as predictors of efficacy and toxicity. The target sample size is 150 patients. The primary endpoint is progression-free survival and secondary endpoints are time-to-failure of strategy, overall survival, response rate, toxicity, and correlations between biomarkers, pre-treatment characteristics and geriatric assessments.

Discussion: The study will add knowledge on how to treat older mCRC patients who are not candidates for standard combination therapy. Furthermore it may provide understanding of efficacy and tolerability of chemotherapy in older cancer patients and thus offer a better chance for tailored treatment strategies in these patients.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Randomized phase II, Non-intensive, SOX, IRIS, Oral, Geriatric assessment, Metastatic colorectal cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-334307 (URN)10.1186/s12885-017-3526-8 (DOI)000408033000001 ()28814275 (PubMedID)
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2017-11-29Bibliographically approved
Hagman, H., Frodin, J.-E. -., Berglund, Å., Sundberg, J., Vestermark, L. W., Albertsson, M., . . . Johnsson, A. (2016). A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial. Annals of Oncology, 27(1), 140-147
Open this publication in new window or tab >>A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial
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2016 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 1, p. 140-147Article in journal (Refereed) Published
Abstract [en]

Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.

Keywords
metastatic colorectal cancer, maintenance treatment, bevacizumab, erlotinib, capecitabine, metronomic chemotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-276825 (URN)10.1093/annonc/mdv490 (DOI)000368354600016 ()
Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2017-11-30Bibliographically approved
Winther, S. B., Osterlund, P., Berglund, Å., Glimelius, B., Qvortrup, C., Sorbye, H. & Pfeiffer, P. (2016). NORDIC9: A randomized phase II trial exploring treatment of older patients with metastatic colorectal cancer (mCRC) by comparing full dose monotherapy (S-1 followed by irinotecan) with reduced combination regimen (S-1/oxaliplatin followed by S-1/irinotecan). Paper presented at 41st Congress of the European-Society-for-Medical-Oncology (ESMO). Copenhagen October 07-11, 2016.. Annals of Oncology, 27(suppl. 6), Article ID 601TiP.
Open this publication in new window or tab >>NORDIC9: A randomized phase II trial exploring treatment of older patients with metastatic colorectal cancer (mCRC) by comparing full dose monotherapy (S-1 followed by irinotecan) with reduced combination regimen (S-1/oxaliplatin followed by S-1/irinotecan)
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2016 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no suppl. 6, article id 601TiPArticle in journal, Meeting abstract (Refereed) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-317513 (URN)10.1093/annonc/mdw370.149 (DOI)000393912500513 ()
Conference
41st Congress of the European-Society-for-Medical-Oncology (ESMO). Copenhagen October 07-11, 2016.
Available from: 2017-04-10 Created: 2017-04-10 Last updated: 2017-11-29Bibliographically approved
Breugom, A. J., van Gijn, W., Muller, E. W., Berglund, Å., van den Broek, C. B., Fokstuen, T., . . . van de Velde, C. J. (2015). Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Annals of Oncology, 26(4), 696-701
Open this publication in new window or tab >>Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial
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2015 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 4, p. 696-701Article in journal (Refereed) Published
Abstract [en]

Background: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo) radiotherapy and total mesorectal excision (TME). Patients and methods: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1: 1) to observation or adjuvant chemotherapy after preoperative (chemo) radiotherapy and TME. Radiotherapy consisted of 5 x 5 Gy. Chemoradiotherapy consisted of 25 x 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Results: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). Conclusion: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo) radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.

Keywords
rectal adenocarcinoma, adjuvant chemotherapy, total mesorectal excision, preoperative radiotherapy, preoperative chemoradiotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-253259 (URN)10.1093/annonc/mdu560 (DOI)000353828700013 ()25480874 (PubMedID)
Available from: 2015-05-26 Created: 2015-05-25 Last updated: 2017-12-04Bibliographically approved
Berglund, Å., Ullen, A., Lisyanskaya, A., Orlov, S., Hagberg, H., Tholander, B., . . . Gullbo, J. (2015). First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies. Investigational new drugs, 33(6), 1232-1241
Open this publication in new window or tab >>First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies
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2015 (English)In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 33, no 6, p. 1232-1241Article in journal (Refereed) Published
Abstract [en]

Purpose Melflufen (melphalan flufenamide, previously designated J1) is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells resulting in selective release and trapping of melphalan, and enhanced activity in preclinical models. Methods This was a prospective, single-armed, open-label, first-in-human, dose-finding phase I/IIa study in 45 adult patients with advanced and progressive solid tumors without standard treatment options. Most common tumor types were ovarian carcinoma (n = 20) and non-small-cell lung cancer (NSCLC, n = 11). Results In the dose-escalating phase I part of the study, seven patients were treated with increasing fixed doses of melflufen (25-130 mg) Q3W. In the subsequent phase IIa part, 38 patients received in total 115 cycles of therapy at doses of 30-75 mg. No dose-limiting toxicities (DLTs) were observed at 25 and 50 mg; at higher doses DLTs were reversible neutropenias and thrombocytopenias, particularly evident in heavily pretreated patients, and the recommended phase II dose (RPTD) was set to 50 mg. Response Evaluation Criteria In Solid Tumors (RECIST) evaluation after 3 cycles of therapy (27 patients) showed partial response in one (ovarian cancer), and stable disease in 18 patients. One NSCLC patient received nine cycles of melflufen and progressed after 7 months of therapy. Conclusions In conclusion, melflufen can safely be given to cancer patients, and the toxicity profile was as expected for alkylating agents; RPTD is 50 mg Q3W. Reversible and manageable bone marrow suppression was identified as a DLT. Clinical activity is suggested in ovarian cancer, but modest activity in treatment of refractory NSCLC.

Keywords
Melphalan flufenamide, Melflufen, J1
National Category
Cancer and Oncology Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-270433 (URN)10.1007/s10637-015-0299-2 (DOI)000365192100009 ()26553306 (PubMedID)
Available from: 2016-02-08 Created: 2015-12-28 Last updated: 2018-01-10Bibliographically approved
Backman, M., Wengstrom, Y., Johansson, B., Sköldengen, I., Hellersted Börjesson, S., Tärnbro, S. & Berglund, Å. (2014). A randomized pilot study with daily walking during adjuvant chemotherapy for patients with breast and colorectal cancer. Acta Oncologica, 53(4), 510-520
Open this publication in new window or tab >>A randomized pilot study with daily walking during adjuvant chemotherapy for patients with breast and colorectal cancer
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2014 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 4, p. 510-520Article in journal (Refereed) Published
Abstract [en]

Background. Physical activity during chemotherapy has been shown in several studies to reduce fatigue, improve symptoms and impact positively on health-related quality of life (HRQoL). Challenges associated with intervention studies on physical activity during cancer treatment relate to consistent adherence. The primary objective was to study feasibility and adherence of physical activity intervention among patients with cancer during adjuvant chemotherapy treatment. The secondary objective was to investigate the effects of physical activity on health aspects, including HRQoL, symptoms and surrogate markers for cardiovascular disease. Material and methods. This randomized controlled trial included patients with breast cancer (BRCA) and colorectal cancer (CRC) during adjuvant chemotherapy. The intervention continued for 10 weeks and included daily walks of 10 000 steps and a weekly supervised group walk. Adherence was assessed by a pedometer and the number of participants who reported step counts every week and percentage of participants who achieved the target steps every week. Results. Adherence average reached 91% during the intervention period; in total 74% completed the exercise intervention. The majority of the participants achieved an average of 83% of the target of 10 000 steps per day for 10 weeks. There was a significant increase in daily physical activity (p = 0.016) in the intervention group. Significant differences were also found for some breast cancer-specific symptoms [swelling, mobility and pain (p = 0.045)]. The study showed a relatively small weight gain an average of 0.9 kg in the intervention group and 1.3 kg in the control group. Conclusion. Physical activity in the form of walking is feasible during adjuvant chemotherapy treatment despite increasing symptoms. The physical activity increased in the intervention group during the study time and had a positive impact on breast symptoms and the weight gain was lower in comparison to previous studies.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-223859 (URN)10.3109/0284186X.2013.873820 (DOI)000333350400010 ()
Available from: 2014-05-09 Created: 2014-04-28 Last updated: 2017-12-05Bibliographically approved
Berglund, Å., Willen, L., Grodeberg, L., Skattum, L., Hagberg, H. & Pauksens, K. (2014). The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab. Acta Oncologica, 53(9), 1212-1220
Open this publication in new window or tab >>The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab
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2014 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 9, p. 1212-1220Article in journal (Refereed) Published
Abstract [en]

It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination. Material and methods. Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal influenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the influenza strains. For the pneumococcal vaccine 14 different serotype-specific anti-capsular antibodies were measured by bead assay xMAP (R). Results. Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI >= 40) to the pandemic-like strain A/California7/2009HINI. After the first and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported. Conclusion. A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to influenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-235332 (URN)10.3109/0284186X.2014.914243 (DOI)000342282100011 ()
Available from: 2014-11-04 Created: 2014-10-30 Last updated: 2017-12-05Bibliographically approved
Johnsson, A., Hagman, H., Frodin, J.-E. -., Berglund, Å., Keldsen, N., Fernebro, E., . . . Jakobsen, A. (2013). A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial. Annals of Oncology, 24(9), 2335-2341
Open this publication in new window or tab >>A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial
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2013 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 9, p. 2335-2341Article in journal (Refereed) Published
Abstract [en]

Background: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC). Patients and methods: Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect. Results: Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B. The rate of any grade 3/4 toxic effect was 53% in arm A and 13% in arm B. Median PFS was 5.7 months in arm A and 4.2 months in arm B (HR = 0.79; 95% confidence interval 0.55-1.12; P = 0.19). Overall survival (OS) from start of induction chemotherapy was 26.7 months in the randomized population, with no difference between the two arms. Conclusions: The addition of erlotinib to bevacizumab as maintenance treatment after first-line chemotherapy in mCRC did not improve PFS significantly. On-going clinical and translational studies focus on identifying subgroups of patients that may benefit from erlotinib in the maintenance setting.

Keywords
metastatic colorectal cancer, bevacizumab, erlotinib, maintenance treatment
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-208361 (URN)10.1093/annonc/mdt236 (DOI)000323963100020 ()
Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-12-06Bibliographically approved
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