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Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Ryhov Cty Hosp, Sweden.ORCID iD: 0000-0002-9845-1410
Ryhov Cty Hosp, Sweden.
Kalmar Cty Hosp, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.ORCID iD: 0000-0002-8015-5728
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2019 (English)In: BMC Cancer, E-ISSN 1471-2407, Vol. 19, article id 40Article in journal (Refereed) Published
Abstract [en]

BackgroundIn the recent phase III trial MPACT the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed increased overall survival compared to gemcitabine alone in the treatment of advanced pancreatic ductal adenocarcinoma (aPDA). Until now there has been limited information on the clinical benefit and toxicity of the combination regimen in a real world setting. In addition the value for patients with locally advanced rather than metastatic aPDA has been unclear, since the former category of patients was not included in the MPACT trial.MethodsA multicentre retrospective observational study in the South Eastern Region of Sweden was performed, with the first 75 consecutive patients diagnosed with aPDA (both locally advanced and metastatic disease) who received first-line treatment with Gem/NabP.ResultsIn the overall population median progression free survival (PFS) and overall survival (OS) were 5.2 (3.4-7.0 95% CI) and 10.9 (7.8-14.0 95% CI) months, respectively. Patients with metastatic disease displayed a median OS of 9.4 (4.9-13.9) and a median PFS of 4.5 (3.3-5.7) months whereas the same parameters in the locally advanced subgroup were 17.1 (7.6-26.6) and 6.8 (5.2-8.4) months, respectively. Grade 3-4 hematologic toxicity was recorded: Neutropenia, leukopenia, thrombocytopenia, and anaemia were observed in 23, 20, 5, and 4% of patients, respectively. Dose reductions were performed in 80% of the patients.ConclusionThis study confirms the effectiveness and safety of first-line Gem/NabP in both locally advanced and metastatic PDA in a real world setting.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 19, article id 40
Keywords [en]
Pancreatic cancer; Chemotherapy; Gemcitabine; Nab-paclitaxel; Bone marrow toxicity
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-154101DOI: 10.1186/s12885-018-5244-2ISI: 000455206800011PubMedID: 30621618OAI: oai:DiVA.org:liu-154101DiVA, id: diva2:1283657
Note

Funding Agencies|Futurum, Academy for Health and Care Jonkoping County Council [695491]; Medical Research Council of Southeast Sweden [FORSS-751541]; ALF grants Region Ostergotland [LIO-697991, LIO- 707011, LIO-697461]; Swedish Cancer Society; Sveriges Gastro-Onkologiska Forening (GOF)

Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2024-10-14
In thesis
1. Prognostic aspects of localised and metastatic pancreatic cancer
Open this publication in new window or tab >>Prognostic aspects of localised and metastatic pancreatic cancer
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest and most treatment resistant types of cancer. Annually, 1500 persons are diagnosed with PDAC in Sweden and just as many succumb to the disease. In the last 15 years there has been a slow change for the better with new more effective treatment combinations for both the postoperative and palliative settings, as well as neoadjuvant approaches in borderline resectable cases and consequently five-year survival has slowly risen to almost 10% in Sweden.

The two main additions to the treatment toolbox, the combination chemotherapy regimens FOLFIRINOX and Gemcitabine/nab-paclitaxel (GnP), both came at the expense of increased toxicity. One of these, GnP, showed less than two months median survival benefit in the underlying randomized controlled trial, and as many PDAC patients are frail and old, the first aim of this thesis was to establish real-world evidence on this treatment and find potential prognostic markers associated with survival benefit in this treatment group.

Survival among the 75 first GnP treated patients in the Swedish South East health care region was almost a year (10.9 months) (Paper I) and the frequency of bone marrow toxicity was lower than expected. High pre-treatment S-Albumin and old age was associated with improved survival (Paper II) encouraging the use of this treatment in older patients.

The second half of this thesis focuses on PDAC in the postoperative setting. In the minority of PDAC patients with resectable disease more than 75% have relapses within two years despite curative intent surgery and adjuvant chemotherapy. Alternatives to Gemcitabine treatment have emerged in the adjuvant setting, mainly including FOLFIRINOX and GemCape. As there are no predictive markers available, prognostic information has become more important to guide the clinical decision making.

In a large retrospective cohort, representing a decade of pancreatic resections in the Swedish South East health care region, we show that the prognostic value of resection margin status can be sharpened by subdividing microscopically non-radical resections by margin distance as well as margin type. Furthermore, the relapse-free and overall survival in patients with extensive spread to lymph nodes, i.e. metastases in the para-aortal lymph nodes (PALN), were very poor. The benefit of surgery in this group of patients is questionable and should be subject for prospective trials (Paper III). To assess tissue based biomarkers a tissue microarray (TMA) based on this cohort as well as cohorts of PDAC resection specimens from the Swedish North and West health care regions was produced. The expression of dihydropyrimidine dehydrogenase (DPD), a key enzyme in the metabolism of antimetabolites, was assessed in the TMA with immunohistochemistry. DPD showed prognostic value in Gemcitabine treated patients, with poor survival in tumours with high DPD expression, but not in the untreated patient group (Paper IV).

In conclusion, outcomes in PDAC are slowly improving but are still among the worst in class. Continued efforts in all aspect of PDAC disease are essential, especially in early detection, development of better drugs, and biomarkers to guide in treatment decisions.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. p. 89
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1922
Keywords
Pancreatic ductal adenocarcinoma, Real-world evidence, Prognostic marker, S-albumin, Resection margin status, PALN, Tissue microarray, DPD
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-208493 (URN)10.3384/9789180756822 (DOI)9789180756815 (ISBN)9789180756822 (ISBN)
Public defence
2024-11-15, Berzeliussalen, Building 463, Campus US, Linköping, 09:00
Opponent
Supervisors
Note

Funding agencies: Futurum - the Academy of Healthcare - Jönköping County Council; The Health Research County in the South-East of Sweden (FORSS); ALF grants from Region Östergötland; RFoU grants from the Department of Clinical Pathology, Region Östergötland; Research grants for resident physicians from Region Östergötland; Lion's Research Fund, Linköping

Available from: 2024-10-14 Created: 2024-10-14 Last updated: 2024-10-14Bibliographically approved

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