Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.
OBJECTIVE
To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities.


METHODS
One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone.


RESULTS
Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect.


CONCLUSIONS
Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.
Radiation Oncology Department, Newcastle Mater Misericordiae Hospital, New South Wales, Australia.
J W
JW
Denham
C S
CS
Hamilton
D
D
Christie
M
M
O'Brien
A
A
Bonaventura
J F
JF
Stewart
S P
SP
Ackland
D S
DS
Lamb
N A
NA
Spry
P
P
Dady
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D018787:Radiation Oncology; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects
D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate