1. Susman, Ed

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SINGAPORE-Doctors should be alert for opportunistic infections among breast cancer patients undergoing dose dense chemotherapy-especially if those patients are receiving steroids as part of prophylactic control of nausea and vomiting side effects, researchers suggested here at the 2015 European Society of Medical Oncology Asia Cancer Symposium.

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

In a retrospective review, Japanese researchers found that as many as 7 percent of the women treated with dose dense chemotherapy since 2014 have been diagnosed with Pneumocystis jiroveci pneumonia, an opportunistic lung infection often reported among individuals with depressed immune systems.


Study Specifics

In a poster presentation at the meeting, Jun Masuda, MD, a resident in Medical Oncology at Toranomon Hospital, Tokyo, said, "We should consider reducing steroids used as anti-emetics for chemotherapy and providing P. jiroveci pneumonia prophylaxis for high-risk patients."


Masuda told OT, "In this study, the incidence of P. jiroveci pneumonia was 7.1 percent among patients treated with dose dense chemotherapy, whereas no P. jiroveci pneumonia was diagnosed among patients treated with a non-dose dense regimen."


The dose dense regimen consisted of doxorubicin 60mg/m2 and cyclophosphamide 600 mg/m2 on day 1 and pegfilgrastim 3.6mg on day 2, every two weeks for four cycles (ddAC). That was then followed by treatment with a taxane, either paclitaxel or docetaxel. The alternative treatment was 5-fluorouracil 500 mg/m2 plus epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 every three weeks for four cycles (FEC), also followed by taxane therapy.


Masuda noted that the finding of P. jiroveci pneumonia in his patients on dose dense chemotherapy is in line with other studies. Nineteen cases with P. jiroveci pneumonia were identified among breast cancer patients treated with AC-containing regimens at Dana-Farber Cancer Institute/Brigham and Women's Hospital from 2000 to 2013, he said.


"Waks AG et al (pubmed/26420402) reported that the risk of Pneumocystis jiroveci pneumonia appeared unique to dose dense chemotherapy," he noted. "Among patients who received ddAC, cumulative incidence of Pneumocystis jiroveci pneumonia was 0.6 percent, while no patients treated with AC in a non-dose-dense schedule developed Pneumocystis jiroveci pneumonia."



In commenting on the study, Eleonora Teplinsky, MD, a medical oncologist at Northwell Health Cancer Institute, Lake Success, New York, told OT: "Dose-dense AC chemotherapy is routinely used in women receiving neoadjuvant or adjuvant chemotherapy for breast cancer. Dose-dense AC (given every two weeks) improves clinical outcomes significantly when compared to non-dose-dense AC (given every three weeks).


"However," she continued, "it is a highly emetogenic regimen and several drugs, including steroids, are given to patients to minimize nausea/vomiting. Removing steroids from the anti-emetic regimen will worsen toxicities for patients. It is important to recognize the potential side effects of steroids, including Pneumocystis jiroveci pneumonia, especially in high risk patients."

Jun Masuda, MD. We s... - Click to enlarge in new windowJun Masuda, MD. "We should consider reducing steroids used as anti-emetics for chemotherapy and providing

Teplinsky said that dose dense chemotherapy is weight based and steroid guidelines are the same, so it seems unlikely that differences in ethnicity would play a role in development of the opportunistic infection.


Study Participants

Masuda said the use of dose dense regimens in Japan is a relatively new phenomenon made possible by the approval in his country of pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor approved for prophylaxis of febrile neutropenia in Japan in September 2014. "Since then, ddAC followed by taxane, one of the global standard regimens for early breast cancer, became available," he said.


"We retrospectively reviewed data of consecutive patients with early breast cancer (stage 1-3), who received ddAC-taxane or FEC-taxane as neoadjuvant or adjuvant chemotherapy in our institute between January 2014 and November 2015," he explained. During that time frame, 28 patients were treated with ddAC and 33 were administered FEC.


The median age for the ddAC cohort of women was 46 years; those receiving FEC had a median age of 49 years. All the patients in the study were given a performance status of 0. Almost all the women were diagnosed as having invasive ductal carcinoma. Two women in the ddAC group were diagnosed with invasive lobular carcinoma; one woman in the FEC treated group had invasive lobular carcinoma.


About two-thirds of the patients in each arm of the study were diagnosed with stage 2 breast cancer. About three-fourths of the tumors ranged in size from 2 centimeters to 5 centimeters, the researchers reported.


In the two women who developed P. jiroveci pneumonia, neither had lung comorbidities before starting their breast cancer regimen. A 65-year-old woman developed the opportunistic infection 46 days after beginning chemotherapy. She completed three cycles of chemotherapy. The second patient, a 56-year-old woman, completed four cycles of chemotherapy before contracting pneumonia on day 72, following initiation of chemotherapy. They were both taking about 2 mg/day of dexamethasone as an anti-emetic and both improved on antibiotic therapy.


"Although this retrospective study suggests that ddAC-taxane is feasible in Japanese women with early breast cancer, we need to be careful about the possible development of Pneumocystis jiroveci pneumonia," Masuda said.