A phase I/II trial of pemetrexed plus radiotherapy in elderly patients with locally advanced non-small cell lung cancer

  • Akihiro Tamiya
  • Masahiro Morimoto
  • Shoichi Fukuda
  • Yoko Naoki
  • Tatsuya Ibe
  • Kyoichi Okishio
  • Hideto Goto
  • Akihiro Yoshii
  • Toshiyuki Kita
  • Naoyuki Nogami
  • Yuka Fujita
  • Shinji Atagi
PHASE II STUDIES
  • 82 Downloads

Summary

Background Radiotherapy (RT) is an effective treatment for elderly patients with locally advanced non-small-cell lung cancer (NSCLC); however, no clinical trials have investigated combination RT with pemetrexed (PEM) in chemotherapy-naive patients ≥71 years old. We conducted a phase I/II study to evaluate the appropriate PEM dose, efficacy, and safety of PEM plus RT in elderly patients. Methods Patients ≥71 years with performance status (PS) scores of 0–2 who had pathologically confirmed stage IIIA/IIIB NSCLC received PEM (500 mg/m2 on day 1 of a 28-day cycle, 4 courses) and RT (a single 2 Gy daily fraction on 5 consecutive days weekly from day 1; 60 Gy total). The primary endpoint was the objective response rate (ORR); the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results Forty-one patients with a median age of 79 years were enrolled; 31 were men. Eighteen patients had squamous cell carcinoma, 27 had stage IIIA disease, and 38 had PS scores 0–1. The ORR was 80.5%, while the median OS and PFS rates were 24.9 and 6.9 months, respectively. Two treatment-related deaths occurred owing to RT-related pneumonitis and severe infection, respectively. Common hematological AEs were leucopenia and neutropenia; common non-hematological AEs were anorexia and constipation. Three patients developed PEM-induced interstitial lung disease; however, most AEs were RT-related. Conclusions Combination PEM and RT shows promising efficacy but relatively severe RT-related toxicities. Therefore, this treatment should be prescribed to elderly patients with caution. Trial registration UMIN 000005036.

Keywords

Pemetrexed Radiotherapy Geriatric patients Pneumonitis 

Abbreviations

AEs

adverse events

ALT

alanine transaminase

AST

aspartate aminotransferase

CBDCA

carboplatin

CDDP

cisplatin

CRT

chemoradiotherapy

CT

computed tomography

DLT

dose limiting toxicity

EGFR

epidermal growth factor receptor

Fr

fraction

Gy

gray

MTD

maximum tolerated dose

NSCLC

non-small cell lung cancer

ORR

objective response rate

OS

overall survival

PD

progression disease

PEM

pemetrexed

PFS

progression-free survival

PS

performance status

RD

recommended dose

RECIST

Response Evaluation Criteria in Solid Tumors

RT

radiotherapy.

Notes

Acknowledgements

We wish to thank all the participants (patients, patients’ family and caregivers) of this study.

Compliance with ethical standards

Conflict of interest

About this study, all authors received the grant from national cancer hospital organization as a research fee (the national hospital organization network program). And all authors report no conflicts of interest in this work.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The institutional research committee is Clinical trial review board of Kinki-chuo Chest Medical Center, and the approved number is 305.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Akihiro Tamiya
    • 1
  • Masahiro Morimoto
    • 2
  • Shoichi Fukuda
    • 1
  • Yoko Naoki
    • 1
  • Tatsuya Ibe
    • 3
  • Kyoichi Okishio
    • 1
  • Hideto Goto
    • 4
  • Akihiro Yoshii
    • 5
  • Toshiyuki Kita
    • 6
  • Naoyuki Nogami
    • 7
  • Yuka Fujita
    • 8
  • Shinji Atagi
    • 1
  1. 1.Department of Internal MedicineNational Hospital Organization Kinki-chuo Chest Medical CenterSakai-cityJapan
  2. 2.Osaka International Cancer InstituteOsaka-cityJapan
  3. 3.National Hospital Organization Nishisaitama-chuo National HospitalTokorozawa-cityJapan
  4. 4.National Hospital Organization Yokohama Medical CenterYokohama-cityJapan
  5. 5.National Hospital Organization Shibukawa Medical CenterShibukawa-cityJapan
  6. 6.National Hospital Organization Kanazawa Medical CenterKanazawa-cityJapan
  7. 7.National Hospital Organization Shikoku Cancer CenterMatsuyama-cityJapan
  8. 8.National Hospital Organization Asahikawa Medical CenterAsahikawa-cityJapan

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