환자 중에서 Lung cancer로 CCRT를 시행했던 분인데, 8월 10일부터 시작하였으니
약 3개월 정도 지났구나. 이정도 시기쯤에 가장 잘온다고 합니다.
11월 23일 내원하여 시행한 X-ray 상에서, 9월 16일에 check 했을 때
관찰되지 않던 병변이 보이고 있습니다.(Lt. mid~lower lung field)
결국 이분은 시행 예정이었던 2nd Taxol-cis consolidation CTx.는 Hold.
일단 Radiation pneumonitis가 좋아지는 것을 보고 하기로 하였습니다.
Prof. ㅈㅁㅎ "Steroid 쓰고 봅시다."
R1. ㄱㅅㄱ "교수님 그럼 용량은...?"
Prof. ㅈㅁㅎ "60mg이나 80mg 쯤 줘보이소."
R1. ㄱㅅㄱ "예 알겠습니다."
사실 잘 모르겠습니다 -_-;;
Steroid라고 하는 것이 종류와 역가가 워낙 다양한지라
뭘 줘야할지도 잘 모르겠고...
그래서 고민을 하다 이 친구 저 친구 전화를 돌려보았으나
뾰족한 답을 듣지 못하였습니다.
R1 ㅂㄷㅎ "저널을 한번 찾아보던지."
R1 ㄱㅅㄱ '그게 귀찮으니까 전화해서 물어보고있지 -_-;;;;'
그래서 결국 생각난 김에 Radiation pneumonitis에 대해 찾아보았습니다.
전반적 내용은 워낙 방대하므로 치료 부분만 보았는데요.
결국 치료의 핵심은 Steroid입니다.
Predinisone(PO제제는 그 흔하게 쓰이는 Solondo입니다)을 최소 60mg/day 씩 2주간 사용한다고 되어있네요.
(역시 교수님이라는 생각을 했습니다)
이후 gradual tapering을 3에서 12주에 걸쳐서 시행하는데, 그에 대한 Guideline이 정립된건 없다합니다.
하지만 Tapering 이후 증상과 Radiologic abnormality가 나타나는 경우가 많다고 하는군요...(어떡하라고!)
이외에 Pentoxifylline은 PLT aggregation을 저해하고, Microvascular blood flow를 개선한다고 되어있군요.
정립된 치료는 없는 듯 합니다.
Collagen Synthesis의 inhibition - Colchicine, penicillamine, Azathioprine, Cyclosporin A가 도움이 된다고 하는데,
Corticosteroid에 tolerable하지 않은 환자에서 고려할 수 있다고 되어있군요.
Amifostine은 신약인 듯 하고...
Captopril은 잘 아시다시피 ACEI입니다. 쥐 모델에서 효과가 있는 것으로 나타났군요. 하지만 사람을 대상으로한
연구에서는 그만한 효과가 안나더라...라고 되어있는데, 일반적으로 잘 쓰는 약이니까 기침이나 신장기능 저하 등
Complication이 없다면 고려해볼만할 듯 합니다.
결국 저의 선택은, 그냥 Solondo 3T(15mg) QID x 2wks...
찾아본데에만 의의를 두도록 하겠습니다.
<UPTODATE 17.1의 원문>
TREATMENT — There are no prospective controlled studies evaluating the efficacy of therapies for radiation pneumonitis in humans. Nevertheless, many experts recommend the use of corticosteroids for symptomatic patients with a subacute onset of radiation lung injury [5,44,45,65] .
Corticosteroids — Prednisone (at least 60 mg/day) is generally given for two weeks, with a gradual taper over three to twelve weeks, although the guidelines for tapering are poorly defined. Corticosteroids may be effective in the treatment of radiation-associated bronchiolitis obliterans organizing pneumonia; however, symptoms and radiographic abnormalities tend to recur with discontinuation of therapy [53] . (See "Cryptogenic organizing pneumonia").
The recommendation for prednisone use is based upon data derived from murine models of radiation pneumonitis that demonstrated a protective effect of corticosteroids [66] . These drugs may reduce radiation pneumonitis via reduction in inflammation, inhibition of TNF-induced nitric oxide-mediated endothelial cell cytotoxicity, or a lymphotoxic mechanism [65] . The prophylactic administration of corticosteroids, antibiotics, or heparin has not been beneficial in reducing the incidence of radiation pneumonitis [5,44,45,54,65] .
Pentoxifylline — Pentoxifylline is a xanthine derivative that inhibits platelet aggregation and enhances microvascular blood flow; it also has immunomodulating and antiinflammatory properties that are probably mediated by inhibition of tumor necrosis factor (TNF) and interleukin 1. Pentoxifylline may have a role for the treatment of radiation-induced fibrosis involving the skin and subcutaneous tissues, and also inhibits experimental bleomycin-induced pulmonary fibrosis in rats, possibly via its anti-TNFa effects. (See "Clinical manifestations and treatment of radiation-induced fibrosis" and see "Bleomycin-induced lung injury").
A modest benefit for pentoxifylline in the prevention of radiation-induced lung toxicity was suggested in a trial in which 40 patients undergoing RT for breast or lung cancer were randomly assigned to pentoxifylline (400 mg three times daily) or placebo during treatment [67] . During six months of follow-up, the number of patients with grade 2 or 3 pulmonary toxicity was significantly less in the pentoxifylline group (20 versus 50 percent). Four patients in the placebo group (30 percent) with grade 3 lung impairment required steroids and oxygen, while only one patient who received pentoxifylline (5 percent) had clinical impairment from grade 2 pulmonary toxicity. The pentoxifylline group had a significantly better diffusing capacity for carbon monoxide at both three and six months following therapy (73 versus 58, and 72 versus 57 percent at three and six months, respectively), but there were no significant differences in spirometry between the two groups. Although intriguing, these results require independent confirmation.
Inhibition of collagen synthesis — Since excess collagen deposition is a key histopathologic feature of radiation fibrosis, drugs that inhibit collagen synthesis, such as colchicine, penicillamine, IFN-gamma, or pirfenidone, may have the potential to modify the progression of fibrosis. However, there are no controlled studies with these agents in humans with radiation-induced lung injury. Azathioprine and cyclosporin A were both effective in treating the symptoms of radiation pneumonitis in single case reports; these agents may be considered in patients who do not tolerate corticosteroids [68,69] .
Amifostine — Amifostine, a cytoprotective agent that appears to shield normal tissues from the toxic effects of chemotherapy and radiotherapy, has been investigated as an agent that may reduce the incidence and severity of radiation pneumonitis [70-74] . Approved as therapy for xerostomia in patients following neck irradiation, amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically-active free thiol metabolite, which can reduce the toxic effects of chemotherapy, and act as a scavenger of free radicals generated in tissues exposed to radiation.
Early evidence suggests that amifostine may decrease radiation-induced pulmonary injury without diminishing the therapeutic effect of radiation. This was demonstrated in a randomized controlled trial of radiation plus amifostine compared to radiation alone in 146 patients with locally advanced lung cancer [71,72] . Amifostine therapy was associated with a significant decrease in pneumonitis (9 versus 43 percent) and also grade 3 esophagitis; in addition, patients receiving amifostine were less likely to have evidence of fibrosis or pneumonitis on chest CT scan (16 versus 49 percent) [71] .
However, these results have not been replicated. In a randomized study involving 243 patients receiving carboplatin, paclitaxel, and thoracic radiotherapy, amifostine did not reduce the rate of grade 3 esophagitis [75] . Rates of pneumonitis in that trial have not been reported.
Captopril — Captopril has been shown to reduce radiation-induced lung fibrosis in rats [76] . One retrospective comparison of the incidence of irradiation-induced lung injury between subjects taking angiotensin converting enzyme (ACE) inhibitors and those who were not, failed to reveal a protective effect from the administration of ACE inhibitors [77] . However, serum concentrations of ACE inhibitors used by subjects in the retrospective human study would be expected to be considerably less than those achieved in the animal model.
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