What is the recommended dose and frequency of iron sucrose (Venofer) for iron deficient anemia related to chemotherapy?

Comment by InpharmD Researcher

The NCCN and Canadian guidelines for management of chemotherapy-induced anemia recommend administering intravenous (IV) iron sucrose 200 mg, which may be repeated every 2 to 3 weeks with close monitoring of iron panels. Alternative dosing regimens may be considered based on individual patient factors with a recommended maximum cumulative dose of 1,000 mg. A recent meta-analysis demonstrated IV iron sucrose, mostly given as a 200 mg single dose after chemotherapy infusion, led to a significantly decreased need for red blood cell transfusion. The long-term safety and efficacy of IV iron in cancer patients need to be further investigated.
Background

The 2018 National Comprehensive Cancer Network (NCCN) guideline on cancer- and chemotherapy-induced anemia recommends the administration of 200 mg intravenous (IV) iron sucrose over 60 minutes. Clinicians can repeat the given dose every 2 to 3 weeks. Alternatively, 200 mg of IV iron sucrose can be administered over 2 to 5 minutes with repeated dosing every 1 to 4 weeks. The panel recommends the total cumulative treatment dose of 1,000 mg and advises against administering individual doses above 300 mg. Repeat iron studies may be considered if treatment with iron fails after 4 to 6 weeks and after the total intended dose has been administered. Subsequent doses of iron should be withheld if the serum ferritin exceeds 800 ng/mL or if the transferrin saturation level exceeds 50%. The panel strongly recommends administering test doses of iron sucrose based on risk factors in patients who demonstrated sensitivities to low-molecular-weight iron dextran, other IV iron preparations, or in patients with multiple drug allergies. [1]

Similar to 2018 NCCN guidelines, 2007 Canadian supportive care recommendations for the management of anemia in patients with cancer suggest administration of 200 mg IV iron sucrose with repeated dosing every 2 to 3 weeks. The Canadian guideline alternatively recommends the administration of 100 mg IV iron sucrose every week for patients where IV administration of iron is warranted. [2]

Given the lack of consensus on administering IV iron in cancer patients undergoing chemotherapy, a 2022 meta-analysis aimed to evaluate the safety and efficacy of IV iron as a monotherapy for the treatment of chemotherapy-induced anemia. A total of 8 randomized controlled trials (N= 1,015) met the inclusion criteria comparing IV iron (n= 553) with either no iron (n= 191) or oral iron supplement (n= 271). Patients who received erythropoiesis-stimulating agents were excluded. Specifically, four trials utilized iron sucrose, mostly given as a 200 mg single dose after chemotherapy infusion for a maximum of 6 weeks. Subgroup analysis based on the type of IV iron preparation found the use of iron sucrose led to a significant decrease in the percentage of patients requiring a red blood cell transfusion (relative risk [RR] 0.67; 95% confidence interval [CI] 0.47 to 0.94). Overall, IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55 to 0.95). Additionally, IV iron was associated with an increased percentage of patients with a hematopoietic response compared with the control (RR 1.23; 95% CI 1.01 to 1.5). Intravenous iron also appeared to be well-tolerated without significantly increasing risks of adverse and severe events. The findings may be limited by the variations in malignant tumors, chemotherapy regimens, and baseline hematologic parameters. Long-term efficacy and safety also remained uncertain, as the longest follow-up duration among included trials was up to 24 weeks. [3]

A 2019 review reported the doses of IV iron sucrose studied in clinical trials on chemotherapy-induced anemia (CIA) were 1 gram, divided into doses of 200 to 300 mg IV infused over 5 to 60 minutes each. Two trials comparing IV iron sucrose with erythropoietin stimulating agent (ESA) versus ESA alone in CIA patients found enhanced ESA response, lower ESA dose, and decreased number of transfusions. In addition, four studies in CIA patients using IV iron sucrose monotherapy also resulted in improved hemoglobin and decreased transfusions. However, the authors reported that at that time, no IV iron formulation had gained Food and Drug Administration approval specifically for the treatment of patients with cancer. [4]

References:

[1] National Comprehensive Cancer Network. Cancer- and Chemotherapy-Induced Anemia (Version 2.2018). Journal of the National Comprehensive Cancer Network. 2018. Accessed October 4, 2022. https://oncolife.com.ua/doc/nccn/Cancer-and_Chemotherapy-Induced_Anemia.pdf
[2] Mikhael J, Melosky B, Cripps C, Rayson D, Kouroukis CT. Canadian supportive care recommendations for the management of anemia in patients with cancer. Curr Oncol. 2007;14(5):209-217. doi:10.3747/co.2007.149
[3] Buchrits S, Itzhaki O, Avni T, Raanani P, Gafter-Gvili A. Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2022;11(14):4156. Published 2022 Jul 18. doi:10.3390/jcm11144156
[4] Rodgers GM, Gilreath JA. The Role of Intravenous Iron in the Treatment of Anemia Associated with Cancer and Chemotherapy. Acta Haematol. 2019;142(1):13-20. doi:10.1159/000496967
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

What is the recommended dose and frequency of iron sucrose (Venofer) for iron deficient anemia related to chemotherapy?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Tables 1-5 for your response.

 

Phase III Randomized Trial Comparing Intravenous to Oral Iron in Patients with Cancer-Related Iron Deficiency Anemia Not on Erythropoiesis Stimulating Agents

Design

Prospective, single-center, open-label, randomized, controlled, phase III trial

N= 192

Objective

 To determine if there is a difference in hematopoietic response in patients treated with oral or intravenous (IV) iron

Study Groups

IV iron (n= 98)

Oral iron (n= 94)

Inclusion Criteria

Patients ≥ 18 years old with malignancy requiring chemotherapy; hemoglobin (Hb) level <12 g/dL with at least one feature indicating iron deficiency (serum ferritin <100 mcg/mL, transferrin saturation <20%, or hypochromic red blood cells >10%); adequate vitamin B12 and folate levels

Exclusion Criteria

History of hypersensitivity to iron; uncontrolled medical illness; taken iron supplements or received blood transfusion within preceding month; prior history of anemia or significant bleeding

Methods

Patients were randomized to receive IV iron (two divided doses of iron sucrose, each diluted with 250 mL of 5% dextrose and administered intravenously over 120 minutes with cycle 1 and cycle 2 of chemotherapy; chemotherapy was 3 weeks apart) or oral iron (100 mg ferrous sulfate capsules three times a day; started with cycle 1 of chemotherapy and continue until the end of cycle 2). Oral iron was allowed to be continued beyond trial completion. The dose of iron sucrose was calculated from the formula for total iron deficit: dose of iron in mg= weight in kg x Hb deficit (13-actual Hb in g/dL) x 2.4 + 500.

Patients were stratified according to malignancy type (solid tumor or hematolymphoid) and level of Hb (≤10 g/dL vs >10 g/dL). 

During the 1st day of weeks 1, 3, and 6, patients were evaluated, took blood tests, and asked to complete a quality of life (QoL) questionnaire (Functional Assessment of Cancer Therapy-Anemia [Fact-An]). Adverse events were recorded at each visit and graded according to Common Terminology Criteria for Adverse Events (CTCAE). 

Duration

Enrollment: March 2010 to March 2015

Follow-Up: Week 1, 3, and 6

Outcome Measures

Primary: change in Hb from baseline to 6 weeks

Secondary: requirement for blood transfusions, quality of life (QoL), response rate to therapy, overall survival (OS), safety profile

Baseline Characteristics

  

IV iron (n= 94)

Oral iron (n= 98)

  

Median age, years (range)

 

55.5 (29-73)

50 (18-73)

  

Female

50 (53.2%) 64 (65.3%)  

Baseline hemoglobin, g/dL (range)

10.2 (7.2-11.9)

10.1 (7.2-12.5)

  

Hematolymphoid

Diffuse Large B-Cell Lymphoma

Burkitt's Lymphoma

Mantle Cell Lymphoma 

4 (4.3%)

4 (4.3%)

0 (0%)

0 (0%)

5 (5.1%)

3 (3.1%)

1 (1%)

1 (1%) 

  

Stage

I

II

III

IV

Unknown

 

2 (2.1%)

14 (14.9%)

33 (35.1%)

45 (47.9%)

0 (0%)

 

4 (4.1%)

15 (15.3%)

26 (26.5%)

52 (53.1%)

1 (1%)

 

Chemotherapy regimen

CHOP *

Platinum-Based 3-Drug Regimen §

Platinum-Based 2-Drug Regimen ¶

Single Agent Chemotherapy

 

4 (4.3%)

6 (6.4%)

82 (87.2%)

2 (2.1%)

 

5 (5.1%)

14 (14.3%)

76 (77.6%)

3 (3.1%)

  

*CHOP: regimen including cyclophosphamide, doxorubicin, vincristine, and prednisolone 

§Platinum-Based 3-Drug included DCF (docetaxel, cisplatin and 5-fluorouracil), ECF (epirubicin, cisplatin and 5-fluorouracil), TIP (paclitaxel, ifosfamide, cisplatin) and BEP (bleomycin, etoposide, cisplatin)

¶Platinum-based 2-drug regimens included various regimens in which platinum was combined with a taxane, pemetrexed, etoposide, doxorubicin, gemcitabine or 5-fluorouracil

Results

Endpoint

IV iron (n= 94)

Oral iron (n= 98)

p-value

Absolute change in Hb at 6 weeks, g/dL

 

n= 87

0.11 ± 1.48

n= 90

-0.16 ± 1.36

 0.23

Requirements for blood transfusion

 

n= 94

13 (9.6%)

n= 98

14 (9.2%)

 1.0

Response rate

53.6%

45.3%

 0.17

Median OS, months

16

20

 0.73

There were no differences in QoL between the two groups.

Adverse Events

Common Adverse Events:

Grade 1: nausea (9% vs. 6%), vomiting (12% vs. 13%), constipation (6% vs. 6%), pain (6% vs. 4%)

Grade 2: nausea (7% vs. 7%), vomiting (2% vs. 6%), diarrhea (8% vs. 9%), pain (3% vs. 8%)

Serious Adverse Events: In the IV iron group (n= 91), three patients had Grade 3 diarrhea (3%), two patients had Grade 3 hypersensitivity (2%), and one patient had Grade 4 hypersensitivity (1%). In the oral iron group (n= 90), 2 patients experienced Grade 3 vomiting (2%) and 6 patients experienced Grade 3 diarrhea (7%).

Percentage that Discontinued due to Adverse Events: Three patients were taken off the study due to ≥ grade 3 hypersensitivity in the IV iron group.

Study Author Conclusions

The study suggests that IV iron is not superior to oral iron in cancer patients on chemotherapy with iron deficiency anemia. 

InpharmD Researcher Critique

Although all patients were deemed iron deficient, only 18.8% of patients responded to treatment. This is possibly due to the myelosuppressive effects of chemotherapy. 



 
References:

Noronha V, Joshi A, Patil VM, et al. Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents. Asia Pac J Clin Oncol. 2018;14(2):e129-e137.

 

Prevention of blood transfusion with intravenous iron in gynecologic cancer patients receiving platinum-based chemotherapy

Design

Open-label, randomized, controlled study

N= 64

Objective

To compare the efficacy of intravenous (IV) iron and oral iron for prevention of blood transfusions in gynecologic cancer patients receiving platinum-based chemotherapy

Study Groups

Oral iron (n= 32)

IV iron (n= 32)

Inclusion Criteria

Ovarian cancer, endometrial cancer, or synchronous ovarian and endometrial cancer; receiving first line platinum-based chemotherapy; age 20–70 years; normal liver and kidney function; no prior radiotherapy; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria

Iron hypersensitivity, risk of iron overload such as chronic renal failure or thalassemia major, and bone marrow metastasis

Methods

Patients were randomized (1:1) to receive 200 mg IV iron sucrose over 30 min immediately after each cycle of chemotherapy or 200 mg oral ferrous fumarate three times a day throughout the six courses of chemotherapy. Chemotherapy regimens included single agent carboplatin and combinations of carboplatin with paclitaxel.

Complete blood counts were monitored before each chemotherapy infusion. Blood transfusions were given prior to chemotherapy administration if hemoglobin level was < 10 mg/dL. Patients received transfusions as follows: one unit for hemoglobin 9 to 9.9 g/dL; two units for hemoglobin 8 to 8.9 g/dL and one additional unit for every 1 g/dL further decline of hemoglobin level.

Duration

June 2011 and December 2012

Treatment: through 6 cycles of chemotherapy

Outcome Measures

Primary: requirement for blood transfusion

Secondary: total number of blood transfusion units, number of cycles requiring blood transfusion, and adverse events

Baseline Characteristics

  

Oral iron (n= 32)

IV iron (n= 32)

 p-value

Age, years

 52.1  ± 10.4 49.7  ± 8.9 0.31

ECOG performance status

0

1

2

 

12 (37.5%)

18 (56.3%)

2 (6.2%)

 

16 (50%)

13 (40.6%)

3 (9.4%)

0.45

Chemotherapy regimen

Carboplatin

Carboplatin with paclitaxel

 

3 (9.4%)

29 (90.6%)

 

1 (3.1%)

31 (96.9%)

0.61

Pre-treatment anemia values

Hemoglobin, g/dL

Hematocrit, %

 

11.4 ± 1.0

35.4 ± 3.0

 

11.3 ± 0.8

35.0 ± 2.4

 

0.72

0.56

Results

Endpoint

Oral iron (n= 32)

IV iron (n= 32)

p-value

Requirement for blood transfusion

18 (56.3%)

9 (28.1%)

0.02 

Median number of total packed red cell units required

0.5

0

0.05

Median number of cycles requiring blood transfusion

0.5

0

0.04

There was no significant difference in mean hemoglobin or hematocrit levels throughout the six cycles of chemotherapy.

Adverse Events

Common Adverse Events: any (56.3% vs. 37.5%), nausea (53.1% vs. 34.4%), vomiting (18.6% vs. 15.6%), bloating (15.6% vs. 0), constipation (40.6% vs. 3.1%; p < 0.001), muscle pain (3.1% vs. 0), pain at injection site (0 vs. 13.3%)

Serious Adverse Events: Neither hypersensitivity reactions nor other serious adverse events were seen in the IV iron group.

Percentage Discontinued due to Adverse Events: None reported

Study Author Conclusions

Intravenous iron administration is an effective treatment for primary prevention of blood transfusions in gynecologic cancer patients receiving platinum-based chemotherapy without serious adverse events. The therapy may be useful as an alternative to oral iron treatment and has the advantage of fewer gastrointestinal side effects in chemotherapy patients.

InpharmD Researcher Critique

 The study is limited by its small sample size. Additionally, as the study only included ovarian or endometrial cancer patients, results may not readily apply to the general oncology patient population.



References:

Athibovonsuk P, Manchana T, Sirisabya N. Prevention of blood transfusion with intravenous iron in gynecologic cancer patients receiving platinum-based chemotherapy. Gynecol Oncol. 2013;131(3):679-682. doi:10.1016/j.ygyno.2013.09.028

 

Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy

Design

Prospective, randomized, observational study

N= 75

Objective

 To examine the impact of intravenously administered iron sucrose on the prevention of anemia in cervical cancer patients undergoing concurrent chemoradiotherapy

Study Groups

Iron sucrose (n= 30)

Control (n= 45)

Inclusion Criteria

 Diagnosed with cervical cancer, developed mild anemia, treated with platinum-based concurrent therapy

Exclusion Criteria

 N/A

Methods

Patients were randomized to receive 10 mL of intravenous (IV) iron sucrose (5,400 mg ferric hydroxide sucrose complex) diluted with 200 mL of normal saline over 30 minutes in the presence of mild anemia or no correction (control group). All patients underwent radiotherapy along with platinum-based chemotherapy consisting of a weekly cisplatin dose of 40 mg per square meter of body surface area (max 70 mg per week) for a total of 6 doses. 

Mild anemia is defined as having a hemoglobin value > 10 g/dL and < 12 g/dL based on complete blood count at the end of each chemoradiotherapy cycle or before therapy began. Patients that experience severe anemia received transfusion with packed red blood cells to reduce side effects.

Duration

October 2003 to December 2005

Treatment: 6 weeks

Outcome Measures

 Need for transfusion (severe anemia), mean transfusion volume, detection of nadir hemoglobin

Baseline Characteristics

  

Iron sucrose (n= 30)

Control (n= 45)

  

Age, years

 55.1 50.1  

Cancer stage

I

II

III

IV

 

8

18 

3 

1 

 

9 

32 

4 

0

  

Tumor size

≤ 4 cm

> 4 cm

 

21 (70.0%)

9 (30.0%)

 

25 (55.6%)

20 (44.4%)

  

Cell type

Squamous cell

Other cell

 

27 (90.0%)

3 (10.0%)

 

40 (88.9%)

5 (11.1%)

  

Initial value

Hemoglobin, g/dL

Hematocrit, %

 

11.27

33.76

 

11.33

33.73

  

Results

Endpoint

Iron sucrose (n= 30)

Control (n= 45)

p-Value

Need for transfusion

12 (40.0%)

29 (64.0%)

0.04

Mean transfusion volume, units

1.87 ± 2.70

2.58 ± 3.89

0.04

Cycle of chemotherapy showing nadir hemoglobin

Initial

After 1st cycle

After 2nd cycle

After 3rd cycle

After 4th cycle

After 5th cycle

After 6th cycle

Total

 

4 (13.3%)

2 (6.7%)

3 (10.0%)

5 (16.7%)

2 (6.7%)

8 (26.6%)

6 (20.0%)

30 (100%)

 

10 (22.2%)

2 (4.4%)

6 (13.4%)

11 (24.4%)

9 (20.0%)

7 (15.6%)

0

45 (100%)

 --

Adverse Events

Side effects due to iron sucrose administration were not observed. Acute allergic reactions such as fever and chill were observed in 6 in the iron sucrose group and 7 in the control group.

Study Author Conclusions

This study showed that intravenous supply of iron sucrose could decrease transfusion requirement and increase serum hemoglobin level in patients with cervical carcinoma undergoing concurrent chemoradiotherapy. Therefore, intravenously administered iron sucrose would be effective in the prevention of anemia of cervical cancer patients receiving concurrent chemoradiotherapy.

InpharmD Researcher Critique

 The majority of patients presented with squamous cell stage 2 cancer and were being treated with cisplatin. Other forms of chemotherapy-induced anemia may confer a different efficacy response from iron sucrose.



References:

Kim YT, Kim SW, Yoon BS, et al. Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy. Gynecol Oncol. 2007;105(1):199-204. doi:10.1016/j.ygyno.2006.11.014

 

Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy

Design

Single-center, prospective, randomized, comparative trial

N= 44

Objective

To compare the incidence of repeated red blood cell (RBC) transfusion in anemic gynecologic cancer patients receiving platinum-based chemotherapy and receiving either intravenous or oral iron

Study Groups

Intravenous iron sucrose (n= 22)

Oral ferrous sulfate (n= 22)

Inclusion Criteria

Aged 20 to 65 years; presence of ovarian cancer, endometrial cancer, or synchronous ovarian and endometrial cancer; met criteria for RBC transfusion (defined as hemoglobin level below 10 g/dL); normal liver and kidney function; no prior radiotherapy or having received radiotherapy; had at least one remaining cycle of chemotherapy

Exclusion Criteria

 Iron hypersensitivity; risk of iron overload such as chronic renal failure or thalassemia major; progressive disease; bone marrow metastasis; and inability to monitor weekly complete blood counts

Methods

Eligible patients who met the criteria for RBC transfusion received transfusion prior to chemotherapy per the hospital's protocol. Transfusion units depended on hemoglobin levels with patients with hemoglobin levels 9 to 9.9 g/dL receiving 1 unit, 8 to 8.9 g/dL receiving 2 units, and one additional unit administered for every 1 g/dL decline of hemoglobin. Study participants were randomized to also receive either 200 mg iron sucrose intravenously over 30 minutes or 200 mg oral ferrous sulfate three times daily. 

Complete blood counts were monitored weekly in both groups and RBC transfusion requirements at the next chemotherapy cycle were noted.

Duration

Chemotherapy receipt period: August 2008 to July 2009

Outcome Measures

Primary outcome: incidence of RBC transfusion at the consecutive cycle of chemotherapy between oral and intravenous iron

Secondary outcomes: hemoglobin and hematocrit increment, number of RBC transfusion units, and adverse events

Baseline Characteristics

  

Oral ferrous sulfate (n= 22)

Intravenous iron sucrose (n= 22)

  

Mean age, years

 53.0  49.6  

Diagnosis

Ovarian cancer

Endometrial cancer

Both ovarian and endometrial cancer

 

86.3%

0

13.6%

 

86.3%

5%

9.1%

  

ECOG performance status

0

1

2

 

13.6%

63.6%

22.7%

 

4.5%

77.3%

18.2% 

  

Regimen

Carboplatin and paclitaxel

Carboplatin

Carboplatin and docetaxel

 

81.8%

9.1%

9.1% 

 

86.4%

9.1%

4.5%

  

Hematology

Hemoglobin 8 to 8.9 g/dL

Hemoglobin 9 to 9.9 g/dL

Mean pretreatment hemoglobin, g/dL

Mean pretreatment hematocrit, %

Median unit of RBC transfusion before treatment

 

40.9%

59.1%

9.0

27.6

1

 

36.4%

63.6%

8.9

27.3

1

  

ECOG, Eastern Cooperative Oncology Group

Results

Endpoint

Oral ferrous sulfate (n= 22)

Intravenous iron sucrose (n= 22)

p-Value

Required RBC transfusion at consecutive cycle

 14 (63.6%) 5 (22.7%) 0.01

Median hemoglobin increment, g/dL (range)

 0.4 (-2.1 to 3.0)  0.9 (-0.9 to 2.6)  0.05

Median hematocrit increment, % (range)

 0.7 (-6.9 to 7.6)   3.1 (-2.4 to 7.9) 0.003

Median unit of RBC transfusion after treatment

 1 (0 to 2) 0 (0 to 2)  0.01 

Adverse Events

Common Adverse Events: mild nausea and vomiting. Other adverse events included headache, muscle pain, constipation, abdominal bloating, and pain at the injection site. There were no significant differences in adverse events between groups.

Serious Adverse Events: None

Percentage that Discontinued due to Adverse Events: All patients were retained throughout the study duration.

Study Author Conclusions

In conclusion, intravenous iron is an alternative treatment for anemic gynecologic cancer patients receiving platinum-based chemotherapy. It is effective in increasing hemoglobin levels and reducing the requirement of RBC transfusions without serious adverse events.

InpharmD Researcher Critique

 The study included only female patients with specific cancer types and specific cancer regimens, which may limit generalizability to other patients. Additionally, although the unit of RBC transfusion was statistically significantly different between both groups, this was not the case for the hemoglobin increment between groups. 



References:

Dangsuwan P, Manchana T. Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy. Gynecol Oncol. 2010;116(3):522-525. doi:10.1016/j.ygyno.2009.12.004

 

Is there any role of intravenous iron for the treatment of anemia in cancer?

Design

Retrospective, chart review study

N= 63

Objective

 To assess the efficacy of intravenous (IV) iron administration for the correction of anemia, the prevention of exacerbation of anemia, decreasing blood transfusion rates, and the survival of cancer patients

Study Groups

 Study participants (N= 63)

Inclusion Criteria

 Patients with various malignancies, received IV iron during cancer treatment (treatment with chemotherapy, radiotherapy, or both), hemoglobin (Hgb) levels between ≥ 9 g/dL, and ≤ 10 g/dL, did not receive red blood cell transfusion before

Exclusion Criteria

 Patients with cancer not receiving treatment or not regularly followed up after treatment

Methods

Patient medical records were retrospectively evaluated. Adminstered IV iron consisted of 100 mg iron sucrose (Venofer®) in 100 mL of saline solution, within 30 minutes of infusion time, 5 infusions every other day. A number of chemotherapy combination strategies could be utilized, with docetaxel+cisplatin (± fluorouracil) being the most common. Radiotherapy areas also varied.

Duration

 Data collection period: January 2009 to January 2015

Outcome Measures

Characteristics of mean hemoglobin, ferritin, and iron levels before and after IV iron sucrose

Patients who experienced further decrease in Hgb levels despite treatment and required blood transfusion, 1-year overall survival rate, mean serum levels after IV iron treatment, correlation between IV iron treatment and tumor response in metastatic patients

Baseline Characteristics

  

Study participants (N= 63)

      

Median age, years

 56      

Female

34 (54%)      

Treatment type

Adjuvant or curative

Metastatic

 

27 (42.9%)

36 (57.1%)

      

Cancer type

Gastrointestinal cancer

Breast cancer

Lung cancer

Other

 

20 (31.7%)

15 (23.8%)

11 (17.5%)

17 (27%)

      

Mean serum levels before IV iron

Hemoglobin, g/dL

Serum ferritin, ng/mL

Serum iron, mcg/dL

 

9.33

156

35.9

      

Results

Endpoint

Study participants (N= 63)

      

Experienced further decrease within 3 months in Hgb levels despite treatment

19 (30%)

      

Required blood transfusion

 18 (28.5%)      

1-year overall survival rate

Responders

Non-responders

p-Value

 

61.1%

35.3%

0.005

      

Mean serum levels based on month range

 Baseline 1-3 months results 6-12 months results p-Value

Hemoglobin, g/dL (range)

9.33 (9 to 10)

 10.4 (8.6 to 13.4) 11.2 (8.2 to 15.1) <0.001

Serum ferritin, ng/mL (range)

156 (2 to 943)

 298.6 (6.4 to 1131) 296.7 (8 to 1600) <0.001

Serum iron, mcg/dL (range)

 35.9 (9 to 107) 71.6 (10 to 276) 67.7 (10 to 235) <0.001

Reduced response to IV iron treatment was correlated with reduced tumor response to cancer therapy in patients with metastatic disease (p< 0.001). Seventeen of 18 metastatic patients who did not respond to IV iron also did not respond to cancer treatment.

Study Author Conclusions

IV iron administration in cancer patients undergoing active oncologic treatment is an effective and safe measure for correction of anemia, and prevention of worsening of anemia. Amelioration of anemia and increase in hemoglobin levels with IV iron administration in patients with disseminated cancer is associated with increased tumor response to oncologic treatment and overall survival. Response to IV iron may be both a prognostic and a predictive factor for response to cancer treatment and survival.

InpharmD Researcher Critique

 The study was retrospective without a proper control group (patient values pre-treatment were utilized). A broad range of cancer patients were allowed for inclusion with over half representing gastrointestinal and breast cancer. 



References:

Gemici C, Yetmen O, Yaprak G, et al. Is there any role of intravenous iron for the treatment of anemia in cancer?. BMC Cancer. 2016;16(1):661. Published 2016 Aug 20. doi:10.1186/s12885-016-2686-2