Timing of Influenza Vaccination in Patients Receiving Chemotherapy

Abstract & Commentary

By William B. Ershler, MD

Synopsis: For patients in the midst of chemotherapy, there are little data on the most efficacious time to administer influenza vaccine. In a randomized study of 38 patients receiving FEC chemotherapy for adjuvant treatment of breast cancer, it is apparent that vaccination early (on day 4 of a 21-day cycle) provided better antibody response than when administered late in the cycle (day 16). Neither group (early or late vaccination) achieved the antibody response of that observed for healthy (and younger) controls. Current advice is to vaccinate well before the initiation of chemotherapy, but for those who are currently receiving drug, the data would suggest treatment early in the cycle rather than late provides the best chance for achieving protective levels of antibody.

Source: Meerveld-Eggink A, et al. Response to influenza virus vaccination during chemotherapy in patients with breast cancer. Ann Oncol 2011;22: 2031-2035.

Oncologists are well aware of the need for influenza vaccination among their patients. Both the presence of malignancy and the immunosuppressive effects of chemotherapy render patients at increased risk for either or both protracted morbidity or mortality from influenza infection. The infection occurs in cancer patients at a rate 3-5 times greater, and mortality from influenza is four times greater than the general population.1 Despite the immunosuppressive effects of chemotherapy, due to the seasonal nature of influenza, and the short-lived protection conferred by the current vaccine preparations, physicians must contemplate when it is optimal to administer the vaccine. However, there is little information available about vaccine timing in the context of the chemotherapy schedule.

To address this issue, a number of investigators throughout the Netherlands conducted a prospective, randomized trial among breast cancer patients receiving adjuvant chemotherapy. Such patients received influenza vaccination during FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-containing chemotherapy regimens (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) six cycles or FEC three cycles followed by docetaxel (100 mg/m2) three cycles. The vaccine used was that prescribed for 2009 which included 15 ug hemagglutinin of the following influenza strains: A/Brisbane/10/2007 (H3N2)-like strain, A/Brisbane/59/2007 (H1N1)-like strain, and B/Brisbane/60/2008-like strain.

Patients were randomized for early (day 4) or late (day 16) vaccination during the chemotherapy cycle. Influenza virus-specific antibody titers were determined before and 3 weeks after vaccination by standard assay (hemagglutination inhibition).

The study enrolled 38 breast cancer patients (20 in the early and 18 in the late group) and 21 healthy controls. The antibody response to influenza vaccination in the patient group as a whole was significantly lower than in the control group. In the early patient group (those vaccinated on day 4 of the chemotherapy cycle) and in the control group, the geometric mean titer (GMT) post-vaccination increased significantly for all three virus strains of the trivalent vaccine. In the late patient group (those vaccinated on day 16 of the chemotherapy cycle), a statistically significant increase in GMT post-vaccination was only found for the H1N1 virus strain.

Patients vaccinated at day 4 tended to have higher antibody titers as compared with patients vaccinated at day 16, although the difference in post-vaccination titers did not reach statistical significance. Geometric mean titers post-vaccination for day 4 vs day 16 were 63.7 vs 29.5 (H3N2), 28.2 vs 19.6 (H1N1), and 29.8 vs 16.0 (B/Brisbane), respectively.

Commentary

As would be expected, patients on chemotherapy have significantly lower responses to influenza virus vaccination compared with healthy controls. Thus, it remains prudent to vaccinate before the initiation of chemotherapy if at all possible.2,3 Yet, due to the seasonal nature of influenza epidemics and the clinical oncology imperative of timely initiation and avoidance of delays in chemotherapy, clinicians are often in the midst of prescribed cancer treatment when influenza vaccines become available and epidemics are looming. The important finding from this small study is that vaccination early during the chemotherapy cycle induces better responses than vaccination later in the cycle. The result is curious and runs counter to what might have been expected. However, the difference might be explained not by the proximity to the prior cycle but to that of the subsequent. Thus, patients vaccinated on day 4 had 17 days before the next exposure to cytotoxic drugs whereas those vaccinated on day 16 would receive chemotherapy in only 5 days, at a time when the optimal vaccine response depends on a healthy immunoproliferative response. In any event, the study was small, and was confined to breast cancer patients receiving one combination of drugs (FEC) and thus generalization to all the variables we confront in our clinics is premature. If nothing else, the study reminds us of the importance of making certain our patients are vaccinated, and for now there are at least some data suggesting it would be best to vaccinate early in the chemotherapy schedule rather than waiting to just before the next cycle, which I must admit is the practice I had heretofore subscribed.

References

1. Cooksley CD, et al. Epidemiology and outcomes of serious influenza-related infections in the cancer population. Cancer 2005;104:618-628.

2. Melcher L. Recommendations for influenza and pneumococcal vaccinations in people receiving chemotherapy. Clin Oncol (R Coll Radiol) 2005;17:12-15.

3. Sommer AL,et al. Evaluation of vaccine dosing in patients with solid tumors receiving myelosuppressive chemotherapy. J Oncol Pharm Pract 2006;12:143-154.