Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient

BMC Cancer. 2017 Aug 29;17(1):586. doi: 10.1186/s12885-017-3576-y.

Abstract

Background: The FOLFOX regimen, i.e., folinic acid (FOL), fluorouracil (F) and oxaliplatin (OX), is a drug cocktail that is used to treat gastric and colorectal cancers. Despite the concomitant improvements in response rate, duration of response and patient survival, reports of serious toxic pulmonary side effects have progressively emerged.

Case presentation: We describe a patient who was treated with FOLFOX as an adjuvant to a rectosigmoidal resection of a rectosigmoidal carcinoma and who developed respiratory insufficiency requiring mechanical ventilation. Computed tomography (CT) imaging and open lung biopsy findings were compatible with interstitial pneumonia (IP). She received multimodal combination treatment (acetylcysteine, corticosteroids, immune globulins and cyclophosphamide) and survived. We performed a systematic literature search and reviewed all 45 reported cases of FOLFOX-related lung toxicity and/or pulmonary fibrosis for their clinical characteristics and their outcomes related to therapy.

Conclusions: We found that for the 45 cases with available data, the median age was 70 years, and the male-female ratio was 3.5: 1. In the patients exhibiting only mild respiratory symptoms, discontinuation of the culprit drug (oxaliplatin) resulted in a 100% regression of the symptoms. However the prognosis of the respiratory insufficient patient proved to be grim: death occurred in 76.9% of the cases despite conventional treatment with corticosteroids. We therefore urge oncologists and critical care specialists not to limit their interventions to the discontinuation of chemotherapy, artificial ventilation, corticosteroids and glutathione replenishment and to consider the gradual introduction of additional immune-modulating agents whenever life-threatening respiratory symptoms in oxaliplatin-treated patients do not subside; all the more so considering the fact that our analysis showed that every patient who survived intubation and mechanical ventilation experienced a full clinical recovery.

Keywords: Case report and review; Chemotherapy lung; Cyclophosphamide; Drug induced pulmonary toxicity; FOLFOX; Immune globulins; Interstitial lung disease; Interstitial pneumonia; Oxaliplatin toxicity.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / surgery
  • Combined Modality Therapy / methods*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Female
  • Fluorouracil / adverse effects
  • Humans
  • Immunotherapy
  • Leucovorin / adverse effects
  • Lung Diseases, Interstitial / chemically induced
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / therapy*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / adverse effects
  • Prognosis
  • Respiration, Artificial
  • Sigmoid Neoplasms / drug therapy*
  • Sigmoid Neoplasms / surgery
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Organoplatinum Compounds
  • Cyclophosphamide
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol