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3–43 Radiation Pneumonitis in Breast Cancer Patients Treated With Taxanes: Does Sequential Radiation Therapy Lower the Risk?
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Radiation Pneumonitis in Breast Cancer Patients Treated With Taxanes: Does Sequential Radiation Therapy Lower the Risk? Beal K, Hudis C, Norton L, et al (Memorial Sloan-Kettering Cancer Ctr, NY) Breast J 11:317-320, 2005
Abstract.—Taxanes are now routinely used in conjunction with radiation therapy (RT) as adjuvant therapy for breast cancer. Recent publications have reported several cases of radiation pneumonitis (RP) in patients receiving RT and taxane chemotherapy, thus raising concern as to the safety of this combination. To decrease the potential risk of RP, we sequenced RT after taxane chemotherapy with a target interval of 3-4 weeks in two consecutive institutional breast protocols. Forty patients were treated on two adjuvant systemic protocols consisting of modified radical mastectomy (n = 9) or breast-conserving surgery (n = 31), followed by adjuvant doxorubicin, cyclophosphamide, and a sequential taxane (ACT), followed by RT. All patients had either node-positive or high-risk nodenegative breast cancer and were treated between October 2000 and September 2002. Postmastectomy, a median dose of 5040 cGy was delivered to the chest wall. After breast-conserving surgery, a median dose of 4680 cGy was delivered to the breast plus a 1400 cGy boost to the surgical cavity. Information regarding RP was gathered retrospectively by reviewing patient records. With a median follow-up of 28 months (range 6-42 months), no cases of clinical RP were identified and no local failures had occurred. The median time interval for all patients between the completion of chemotherapy and the initiation of RT was 34 days (range 5-70 days). At
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the latest follow-up, 2 patients were diagnosed with metastatic disease and 38 patients were without evidence of disease. Sequencing of RT after taxane therapy with a target interval of 3-4 weeks does not appear to result in increased pulmonary toxicity and is associated with good local control. Clinical trials have indicated that both taxane chemotherapy and RT improve the outcome for a large percentage of patients with invasive breast cancer. It is therefore critical that the treatment schedule for delivery of these therapies be optimized to achieve the highest efficacy and lowest rates of morbidity. Previous small studies have indicated that delivery of RT concurrently with or shortly after paclitaxel results in increased rates of RP.1,2 To further address the effect of sequential paclitaxel/RT scheduling on rates of lung injury, we recently investigated the outcome of 189 patients treated in a clinical trial in which patients were randomly assigned to undergo either 8 cycles of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) or 4 cycles of paclitaxel followed by 4 cycles of FAC.3 This trial also included comparative groups who received similar radiation treatments and had the same total number of chemotherapy cycles. We found that the risk of RP was approximately 5% in both groups, and no statistical differences were found in the rates of pulmonary symptoms. An increased rate of asymptomatic chest x-ray changes consistent with radiation effects was noted in the paclitaxel group, but these changes were not of clinical significance to the patients. The article by Beal and colleagues presented similar findings. In their study, only 40 patients were evaluated, and
Breast Diseases: A Year Book Quarterly Vol 17 No 3 2006
most received radiation only to a breast field, so the volume of lung irradiated was minimal. Some of the patients in this retrospective study received docetaxel, and some received paclitaxel. None of the patients received taxanes concurrently with RT. No cases of RP were found in the review of patient records. Chest x-ray findings were not evaluated. From the available findings, it seems that treatment with sequential taxane and radiation is safe, with a low risk of lung injury. The interval between the 2 therapies may be an important determinant of this risk. The use of taxanes concurrently with radiation should be limited to well-designed clinical trials that carefully and prospectively monitor rates of RP and other normal tissue effects. T. A. Buchholz, MD T.-K. Yu, MD, PhD
References 1. Taghian AG, Assaad SI, Niemierko A, et al: Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 93:1806-1811, 2001. 2. Hanna YM, Baglan KL, Stromberg JS, et al: Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy. Breast J 8:149-153, 2002. 3. Yu T, Whitman GJ, Thames HD, et al: Clinically relevant pneumonitis is not increased in breast cancer patients treated with sequential paclitaxel and radiation. J Natl Cancer Inst 96:16761681, 2004.
Radiation Pneumonitis in Breast Cancer Patients Treated With Taxanes: Does Sequential Radiation Therapy Lower the Risk? Beal K, Hudis C, Norton L, et al (Memorial Sloan-Kettering Cancer Ctr, NY) Breast J 11:317-320, 2005
Abstract.—Taxanes are now routinely used in conjunction with radiation therapy (RT) as adjuvant therapy for breast cancer. Recent publications have reported several cases of radiation pneumonitis (RP) in patients receiving RT and taxane chemotherapy, thus raising concern as to the safety of this combination. To decrease the potential risk of RP, we sequenced RT after taxane chemotherapy with a target interval of 3-4 weeks in two consecutive institutional breast protocols. Forty patients were treated on two adjuvant systemic protocols consisting of modified radical mastectomy (n = 9) or breast-conserving surgery (n = 31), followed by adjuvant doxorubicin, cyclophosphamide, and a sequential taxane (ACT), followed by RT. All patients had either node-positive or high-risk nodenegative breast cancer and were treated between October 2000 and September 2002. Postmastectomy, a median dose of 5040 cGy was delivered to the chest wall. After breast-conserving surgery, a median dose of 4680 cGy was delivered to the breast plus a 1400 cGy boost to the surgical cavity. Information regarding RP was gathered retrospectively by reviewing patient records. With a median follow-up of 28 months (range 6-42 months), no cases of clinical RP were identified and no local failures had occurred. The median time interval for all patients between the completion of chemotherapy and the initiation of RT was 34 days (range 5-70 days). At
270 270
®
the latest follow-up, 2 patients were diagnosed with metastatic disease and 38 patients were without evidence of disease. Sequencing of RT after taxane therapy with a target interval of 3-4 weeks does not appear to result in increased pulmonary toxicity and is associated with good local control. Clinical trials have indicated that both taxane chemotherapy and RT improve the outcome for a large percentage of patients with invasive breast cancer. It is therefore critical that the treatment schedule for delivery of these therapies be optimized to achieve the highest efficacy and lowest rates of morbidity. Previous small studies have indicated that delivery of RT concurrently with or shortly after paclitaxel results in increased rates of RP.1,2 To further address the effect of sequential paclitaxel/RT scheduling on rates of lung injury, we recently investigated the outcome of 189 patients treated in a clinical trial in which patients were randomly assigned to undergo either 8 cycles of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) or 4 cycles of paclitaxel followed by 4 cycles of FAC.3 This trial also included comparative groups who received similar radiation treatments and had the same total number of chemotherapy cycles. We found that the risk of RP was approximately 5% in both groups, and no statistical differences were found in the rates of pulmonary symptoms. An increased rate of asymptomatic chest x-ray changes consistent with radiation effects was noted in the paclitaxel group, but these changes were not of clinical significance to the patients. The article by Beal and colleagues presented similar findings. In their study, only 40 patients were evaluated, and
Breast Diseases: A Year Book Quarterly Vol 17 No 3 2006
most received radiation only to a breast field, so the volume of lung irradiated was minimal. Some of the patients in this retrospective study received docetaxel, and some received paclitaxel. None of the patients received taxanes concurrently with RT. No cases of RP were found in the review of patient records. Chest x-ray findings were not evaluated. From the available findings, it seems that treatment with sequential taxane and radiation is safe, with a low risk of lung injury. The interval between the 2 therapies may be an important determinant of this risk. The use of taxanes concurrently with radiation should be limited to well-designed clinical trials that carefully and prospectively monitor rates of RP and other normal tissue effects. T. A. Buchholz, MD T.-K. Yu, MD, PhD
References 1. Taghian AG, Assaad SI, Niemierko A, et al: Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 93:1806-1811, 2001. 2. Hanna YM, Baglan KL, Stromberg JS, et al: Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy. Breast J 8:149-153, 2002. 3. Yu T, Whitman GJ, Thames HD, et al: Clinically relevant pneumonitis is not increased in breast cancer patients treated with sequential paclitaxel and radiation. J Natl Cancer Inst 96:16761681, 2004.