| 1. |
- Bergqvist, Michael, et al.
(författare)
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Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer
- 2017
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:3, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.RESULTS: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.CONCLUSION: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.
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| 2. |
- Blomberg, Carl, et al.
(författare)
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Randomized Trials of Systemic Medically-treated Malignant Mesothelioma : A Systematic Review
- 2015
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:5, s. 2493-2501
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Forskningsöversikt (refereegranskat)abstract
- Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.
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| 3. |
- Djureinovic, Dijana, et al.
(författare)
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Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer
- 2018
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 125, s. 157-163
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Tidskriftsartikel (refereegranskat)abstract
- Cancer testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies. To comprehensively analyse auto-antibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases. Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analysed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against CT47A genes, PAGE3, VCX, MAGEB1, LIN28B and C12orf54 were only found in NSCLC patients at a frequency of 1%-4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients.In conclusion, we identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets.
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| 4. |
- Holgersson, Georg, et al.
(författare)
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A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer
- 2015
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- AXL1717 is an orally bioavailable IGF-1R pathway modulator that has been shown to have anti-tumoral effects. The objectives of the present study were to define maximum tolerated dose and the recommended phase II dose (RPTD) of AXL1717 in combination with gemcitabine HCl and carboplatin in non-small cell lung cancer (NSCLC). Patients with previously untreated, locally advanced, or metastatic NSCLC (squamous cell cancer or adenocarcinoma) in good performance status and with preserved major organ functions were enrolled in the study. The study was an open-label phase I study with planned cohorts of three patients per dose level of AXL1717 (215, 290, and 390 mg BID). In total, 12 patients were enrolled in the study, and of these, two were prematurely excluded. AXL1717 was administered at one dose level, 215 mg BID. A total number of 81 unique adverse events were reported. Bone marrow toxicity was reported in 10 out of 12 patients, and this organ class showed the largest number of related events. AXL1717 in combination with gemcitabine HCl and carboplatin is a possible treatment approach in previously untreated, locally advanced, or metastatic non-small cell lung cancer. However, due to the bone marrow toxicity profile shown in the present study, further dose increases of AXL1717 above 215 mg BID will probably not be feasible. Therefore, 215 mg BID constitutes maximum tolerated dose and RPTD.
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| 5. |
- Holgersson, Georg, et al.
(författare)
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Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy
- 2015
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 35:10, s. 5491-5497
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC).Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000.Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17).Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.
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| 6. |
- Holgersson, Georg, et al.
(författare)
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[In Process Citation].
- 2015
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- The work-up process for lung cancer patients consists of several steps from suspicion of malignant disease to start of treatment. Delays between these steps should be minimized. Data in the Swedish National Lung Cancer Register show that the work-up times for lung cancer patients vary greatly between different counties in central Sweden. In order to reduce delays, a trial of implementing patient guides (Sw: patientlotsar) for patients referred to the hospital was conducted. When comparing the work-up times before and after implementation of patient guides the median waiting time from suspicion of lung cancer to start of treatment in the region was reduced from 71 to 45 days. Furthermore, the duration of most of the steps in the work-up process were shortened despite more complex investigation procedures, e.g. increased use of PET/CT in the guided patient group.
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| 7. |
- Holgersson, Georg
(författare)
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Prognostic Factors in Non-Small Cell Lung Cancer (NSCLC)
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Non-small cell lung cancer (NSCLC) is the cancer disease with the highest mortality globally. About 75% of NSCLC patients are diagnosed in an advanced stage where surgical treatment is not possible. For patients with locally advanced disease without distant metastases, the treatment of choice is curatively intended radiotherapy. However, this treatment has considerable side effects and many patients relapse. To individualize the treatment strategy for these patients, it is essential to have as much prognostic information as possible. The aim of this thesis was to investigate the prognostic significance of histology and pre-treatment hematopoietic blood parameters.Material and Methods: Data were collected retrospectively for NSCLC patients treated between 1990 and 2000 with curatively intended radiotherapy. The data were obtained by manually searching patient records from all radiation oncology departments in Sweden. The prognostic significance of histology, and pre-treatment levels of hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) were analyzed in relation to overall survival using univariate and multivariate statistical methods. These prognostic factors were further analyzed in a chemoradiation patient cohort and in a cohort of patients with recurrent NSCLC treated with palliative docetaxel, or the insulin-like growth factor 1 receptor (IGF-1R) modulator AXL1717.Results: In the cohort of NSCLC patients treated between 1990 and 2000, squamous cell carcinoma (SCC) histology and pre-treatment anemia (Hgb <110 g/L), leukocytosis (WBC > 9.0 x109/L), and thrombocytosis (Plt >350 x109/L) were independent prognostic factors for shorter overall survival. However, in the chemoradiation cohort only thrombocytosis retained independent prognostic significance in a multivariate analysis. In the cohort of patients with recurrent disease treated with palliative systemic therapy, only leukocytosis was significantly associated with worse survival.Conclusions: Routine pre-treatment hematopoietic blood parameters—together with other prognostic factors such as disease stage and performance status—can provide decision-making support when individualizing treatment of NSCLC. The prognostic role of histology is unclear and further research is warranted to determine its significance.
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| 8. |
- Holgersson, Georg, et al.
(författare)
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The prognostic value of pre-treatment leukocytosis in patients with previously treated, stage IIIB/IV non-small cell lung cancer treated with the IGF-1R pathway modulator AXL1717 or docetaxel : a retrospective analysis of a phase II trial
- 2017
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Ingår i: Asian Pacific Journal of Cancer Prevention. - 1513-7368. ; 18:6, s. 1555-1560
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to investigate any prognostic value of pre-treatment anemia, leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC.Methods: A randomized, multicenter phase II study comparing the IGF-1R modulator AXL with standard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011-2013. Clinical and laboratory data were collected, including serum values for hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) at baseline. These hematological parameters were studied in relation to overall survival using Kaplan-Meier product-limit estimates and multivariate Cox proportional hazards regression models.Results: The median overall survival for all patients was 8.9 months. Patients with leukocytosis (WBC > 9 x 109/L) had a significantly shorter median overall survival (4.2 months) as compared with those with a WBC ≤ 9 x 109/L at baseline (12.3 months) with a corresponding of HR 2.10 (95% CI: 1.29-3.43). Patients with anemia (Hgb < 110 g/L) had a non-significant (p = 0.097) shorter median overall survival (6.1 months) as compared with their counterparts with Hgb ≤ 110 g/L at baseline (9.4 months). As for thrombocytosis (Plt > 350 x 109/L), there was no statistically significant impact on overall survival. Leukocytosis retained its prognostic significance in a multivariate model where other clinical factors such as age, sex and WHO performance status were taken into consideration (HR: 1.83, 95% CI: 1.06-3.13, p = 0.029).Conclusion: Pre-treatment leukocytosis is a strong and independent prognostic marker for shorter overall survival in previously treated stage IIIB or IV NSCLC patients receiving docetaxel or AXL1717. Combined use of pre-treatment leukocytosis assessments together with established prognostic factors such as performance status could be of help when making treatment decisions in this clinical setting.
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| 9. |
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| 10. |
- Holgersson, Georg, et al.
(författare)
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The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy
- 2017
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Ingår i: Neoplasma (Bratislava). - Bratislava : AEPress. - 0028-2685 .- 1338-4317. ; 64:6, s. 909-915
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Tidskriftsartikel (refereegranskat)abstract
- Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109 /L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109 /L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting
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