Received: 10 February 2017 Accepted: 18 June 2017 Published on: 28 August 2017
Phase III randomized trial comparing intravenous to oral iron in
patients with cancer-related iron deﬁciency anemia not on
erythropoiesis stimulating agents
Vijay Maruti Patil
Shripad D. Banavali
Purvish M. Parikh
Department of Medical Oncology, Tata Memo-
rial Hospital, Parel,Mumbai, Maharashtra, India
Department of Medical Oncology, Asian Cancer
Institute, K.J. Somaiya Ayurvihar, Mumbai,
pharmEDGE, Mumbai, Maharashtra, India
Dr.Kumar Prabhash, Department of Medical
Oncology,TataMemorial Hospital, Dr. E Borges
Marg, Parel, Mumbai 400012 India.
TataMemorial Center Research Administra-
tion Council (TataMemorial Center, Mumbai,
Aim: We aimed to ﬁnd the optimal route of iron supplementation in patients with malignancy
and iron deﬁciency (true or functional) anemia not receiving erythropoiesis stimulating agents
Methods: Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) <12 g/dL and
serum ferritin <100 mcg/mL, transferrin saturation <20% or hypochromic red blood cells >10%
were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint
was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, qual-
ity of life (QoL), toxicity, response and overall survival.
Results: A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm.
Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb
at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and −0.16 g/dL (SD: 1.36) in oral
arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in
Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients
(14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade)
developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron
and none on oral iron had hypersensitivity, P = 0.06. QoL was not signiﬁcantly different between
the two arms.
Conclusion: IV iron was not superior to oral iron in patients with malignancy on chemotherapy and
iron deﬁciency anemia.
anemia, blood transfusion, ferric compounds, iron, iron-deﬁciency
Anemia is common in patients with malignancy. Ludwig et al. per-
formed a prospective survey in 15,367 European cancer patients,
and found that at enrolment, the overall prevalence of anemia was
39.3% and patients who received chemotherapy had the highest inci-
dence of anemia at 62.7%.
Anemia in cancer patients is multifacto-
rial; nutritional deﬁciencies (iron, vitamin B
and folate) are important
Iron deﬁciency anemia is one of the commonest forms of nutritional
anemia, characterized by inadequate iron stores. Iron deﬁciency can be
a true or functional deﬁciency. The standard therapy for iron deﬁciency
anemia is iron supplementation, most commonly by oral iron supple-
ments. The established indications for parenteral, that is intravenous
(IV) iron supplementation include failure of oral iron, intolerance to
oral iron, a condition that confers refractoriness to oral iron (e.g.,
post-gastrectomy, celiac disease, atrophic gastritis, H. pylori infection,
etc.), need for rapid anemia reversal (e.g., late in pregnancy, chronic
Asia-Pac J Clin Oncol. 2018;14:e129–e137.
2017 John Wiley & Sons Australia, Ltd e129wileyonlinelibrary.com/journal/ajco