5. 各薬剤のOR
Drug OR Drug OR
Acetaminophen 2.4[1.1-5.2] Erythromycin 7.6[1.1-51.1]
Acetyldigoxin 9.9[2.3-42.0] Indomethacin 8.9[2.9-27.8]
Aprindine 上昇 Methimazole 230.9[120.4-453.5]
Ca dobesilate 77.8[4.5-1346] Phenytoin 11.6[3.1-43.5]
Carbamazepine 5.9-16.9 Prednisone 19.9[10.1-49.7]
Carbimazole 16.7[2.6-69.7] Procainamide 上昇
Cinepazide 上昇 Propranolol 2.5[1.1-6.1]
Clomipramine 20.0[6.1-57.6] Pyrithyldione 200.11[22.62-∞]
Chlorpromazine 15.7[1.3-182] Spironolactone 20.0[2.3-175.9]
Diclofenac 3.9[1.0-15.0] Sulfasalazine 24.8-74.6
Digoxin 2.5-5.9 Ticlopidine 103.2[12.7-837.4]
ST合剤 10.4-25.1
Ann Intern Med 2007;146:657-65
6. • 化学療法と
好中球減少リスク
Table 1. Risk of Febrile Neutropenia, According to the Type of Cancer and Chemotherapy Regimen.*
Risk of Neutropenia and Type of Cancer Chemotherapy Regimen
High risk (>20%)
Bladder cancer MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for neoadjuvant or adjuvant therapy and
metastatic disease
Breast cancer Docetaxel and trastuzumab for metastatic or relapsed disease
Dose-dense ACT (doxorubicin, cyclophosphamide, and paclitaxel) for adjuvant therapy†
Doxorubicin and paclitaxel for metastatic or relapsed disease
Doxorubicin and docetaxel for metastatic or relapsed disease
TAC (docetaxel, doxorubicin, and cyclophosphamide) for adjuvant therapy
Esophageal and gastric cancer Docetaxel, cisplatin, and fluorouracil
Hodgkin’s lymphoma BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)‡
Kidney cancer Doxorubicin and gemcitabine
Non-Hodgkin’s lymphoma CFAR (cyclophosphamide, fludarabine, alemtuzumab, and rituximab) for chronic lymphocytic leuke-
mia with del(17p) and relapsed or refractory disease
ICE (ifosfamide, carboplatin, and etoposide) for diffuse large-B-cell lymphoma, peripheral T-cell lym-
phomas, and second-line or salvage therapy
RICE (rituximab, ifosfamide, carboplatin, and etoposide)
CHOP-14 (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab†
MINE (mesna, ifosfamide, novantrone, and etoposide) for diffuse large-B-cell lymphoma, peripheral
T-cell lymphomas, second-line therapy, and refractory disease
DHAP (dexamethasone, cisplatin, and cytarabine) for diffuse large-B-cell lymphoma, peripheral T-cell
lymphomas, and second-line therapy
ESHAP (etoposide, methylprednisolone, cisplatin, and cytarabine) for diffuse large-B-cell lymphoma,
peripheral T-cell lymphomas, second-line therapy, and recurrent disease
HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus rituximab
Melanoma Dacarbazine-based combination (dacarbazine, cisplatin, and vinblastine) for advanced, metastatic, or
recurrent disease
Dacarbazine-based combination (dacarbazine, cisplatin, and vinblastine) plus interleukin-2 and inter-
feron alfa for advanced, metastatic, or recurrent disease
Multiple myeloma Modified HyperCVAD
Myelodysplastic syndromes Rabbit antithymocyte globulin and cyclosporine
Decitabine
Ovarian cancer Topotecan, paclitaxel, or docetaxel
Sarcoma MAID (mesna, doxorubicin, ifosfamide, and dacarbazine) or doxorubicin
Small-cell lung cancer Topotecan
Testicular cancer VeIP (vinblastine, ifosfamide, and cisplatin)
VIP (etoposide, ifosfamide, and cisplatin)
BEP (bleomycin, etoposide, and cisplatin)‡
TIP (paclitaxel, ifosfamide, and cisplatin)N Engl J Med 2013;368:1131-9.
7. N Engl J Med 2013;368:1131-9.
Table 1. (Continued.)
Risk of Neutropenia and Type of Cancer Chemotherapy Regimen
Intermediate risk (10–20%)
Occult primary adenocarcinoma Gemcitabine and docetaxel
Breast cancer Docetaxel every 21 days
Epirubicin for adjuvant therapy
Epirubicin plus sequential cyclophosphamide, methotrexate, and fluorouracil for adjuvant therapy
CMF classic (cyclophosphamide, methotrexate, and fluorouracil) for adjuvant therapy
AC (doxorubicin and cyclophosphamide) plus sequential docetaxel for adjuvant therapy (during
docetaxel portion only)
AC plus sequential docetaxel and trastuzumab for adjuvant therapy
FEC (fluorouracil, epirubicin, and cyclophosphamide) plus sequential docetaxel
Paclitaxel every 21 days for metastatic or relapsed disease
Vinblastine for metastatic or relapsed disease
Cervical cancer Cisplatin and topotecan for recurrent or metastatic disease
Topotecan for recurrent or metastatic disease
Irinotecan for recurrent or metastatic disease
Colorectal cancer FOLFOX (fluorouracil, leucovorin, and oxaliplatin)
Esophageal and gastric cancer Irinotecan and cisplatin
Epirubicin, cisplatin, and fluorouracil
Epirubicin, cisplatin, and capecitabine
Hodgkin’s lymphoma ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)‡
Stanford V (mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone)‡
Non-Hodgkin’s lymphoma EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) for AIDS-related
disease, Burkitt’s lymphoma, and recurrent disease
EPOCH plus intrathecal chemotherapy for AIDS-related disease, diffuse large-B-cell lymphoma, and
recurrent disease
ACOD (modified CHOP: doxorubicin, cyclophosphamide, vincristine, and prednisone)
GDP (gemcitabine, dexamethasone, and cisplatin) for diffuse large-B-cell lymphoma, peripheral T-cell
lymphomas, and second-line therapy
GDP plus rituximab for diffuse large-B-cell lymphoma and second-line therapy
FM (fludarabine and mitoxantrone)
CHOP plus rituximab, including regimens with pegylated liposomal doxorubicin or mitoxantrone sub-
stituted for doxorubicin
Non–small-cell lung cancer Cisplatin and paclitaxel for adjuvant therapy and advanced or metastatic disease
Cisplatin and vinorelbine for adjuvant therapy and advanced or metastatic disease
Cisplatin and docetaxel for adjuvant therapy and advanced or metastatic disease
Cisplatin and irinotecan for advanced or metastatic disease
Cisplatin and etoposide for adjuvant therapy and advanced or metastatic disease
Carboplatin and paclitaxel for adjuvant therapy and advanced or metastatic disease§
Docetaxel for advanced or metastatic disease
Ovarian cancer Carboplatin and docetaxel
Prostate cancer Cabazitaxel¶
Small-cell lung cancer Etoposide and carboplatin
Testicular cancer Etoposide and cisplatin
Uterine cancer Docetaxel for uterine sarcoma and advanced or metastatic disease
12. 緑膿菌のRisk
• 市中感染症での緑膿菌Risk
• Presentation of Neutropenia OR 2.23[1.05-4.75]
• Presentation with Septic shock OR 2.07[1.09-3.94]
• Indwelling Central Venous Catheter OR 2.93[1.28-6.69]
• Health-care-associated infection OR 11.00[5.10-23.71]
(Am J of Med 2008;121:709-14)
• 緑膿菌Bacteremiaは死亡リスク OR 10.60[3.83-29.30]
(E. coliと比較) (Am J of Med 2008;121:709-14)
30. • 61-80歳のリンパ腫患者でCHOP-Rを行う103名のRCT.
• CHOP-Rは14日毎に行うレジメ(CHOP-14)
• 2wkの化学療法の内, Day 2にPegfilgrastimを投与する群
vs. Day 4に投与する群に割り付け, 好中球減少の頻度を比較.
(化学療法後1日後 vs 3日後投与の比較)
• 好中球はDay 4に投与する群の方が好中球減少の頻度は少なく,
回復も良好
Annals of Oncology 22: 1872–1877, 2011
original article
Table 2. Incidence of leukocytopenia (CTC grade 3 and 4)
Pegfilgrastim
on day 2
Pegfilgrastim
on day 4
P value
CTC 3, 4 (% of cycles)
(<2 · 103
/mm3
)
70.0 43.4 <0.001a
CTC 4 (% of cycles)
(<1 · 103
/mm3
)
47.0 20.5 <0.001a
CTC 3, 4 (% of patients)
(<2 · 103
/mm3
)
84.4 70.3 0.166
CTC 4 (% of patients)
(<1 · 103
/mm3
)
65.6 43.2 0.063
a
Cochrane–Armitage test for trend: P < 0.001.
CTC, Common Toxicity Criteria.
original article
35. HEPA filterのMeta
• 血液腫瘍に対するChemo, 骨髄移植患者を対象とし,
HEPA filter vs non-HEPA filterを使用した換気設備の
真菌感染症予防効果を評価したRCT, non-RCTのMeta.
• 8 RCTs
The Journal of Infectious Diseases 2006;193:1408–18
Table 1. Characteristics of 8 randomized controlled trials included in the meta-analyses.
Authors, year of
publication [reference] Location Outcome Clinical condition(s) of participants Therapy received Portion of participants considered
a
Follow-up duration Additional therapy received
Levine et al., 1973 [27] Bethesda, MD Fungal infection
and death
Acute leukemia Chemotherapy Patients in 2 of 3 study arms 50 days Topical or orificial antiseptics
and antibiotics
Yates et al., 1973 [26] Buffalo, NY Death Acute myeloid leukemia Chemotherapy A portion of the patients evaluated Not mentioned Partial gut sterilization
Schimpff et al., 1975 [21] Baltimore, MD Fungal infection Acute myeloid leukemia Chemotherapy Patients in 2 of 3 study arms 120 days Oral nonabsorbable
antibiotics
Buckner et al., 1978 [24]
b
Seattle, WA Fungal infection
and death
Aplastic anemia plus acute
leukemia; acute leukemia only
BMT For fungal infection as the outcome,
all participants; for death as the
outcome, a portion of the participants
6 months to 4 years Oral nonabsorbable
antibiotics
c
Lohner et al., 1979 [32] Brussels, Belgium Fungal infection Acute leukemia, agranulocytosis,
lymphosarcoma
Chemotherapy All Not mentioned Oral nonabsorbable
antibiotics
Storb et al., 1983 [25] Seattle, WA Death Aplastic anemia BMT All 16 months to 11 years Oral nonabsorbable
antibiotics
c
Petersen et al., 1987 [29] Seattle, WA Death All diseases that make BMT
necessary
BMT All 100 days Prophylactic systemic
antibiotics
Petersen et al., 1988 [28] Seattle, WA Death All diseases that make BMT
necessary
BMT Patients in 2 of 4 study arms 30 days Prophylactic systemic anti-
biotics or nonabsorbable
antibiotics
36. • 8 non-RCTs
• アウトカム; 死亡率, 真菌感染率に有意差無し.
Table 2. Characteristic of 8 nonrandomized controlled trials included in the meta-analyses.
Authors, year of publication
[reference] Location Outcome
Clinical condition(s)
of participants Therapy received
Portion of study participants
considered
a
Follow-up duration Additional therapy received
Rodriguez et al., 1978 [23]
b
Houston, TX Fungal infection
and death
Acute leukemia Chemotherapy All 10 months to 4 years Oral antibiotics and
systemic antibiotics
Navari et al., 1984 [33]
c
Seattle, WA Fungal infection Aplastic anemia BMT Patients in 2 of 3 study arms 100 days None
Rhame et al., 1984 [34] Minneapolis, MN Fungal infection All diseases that make
BMT necessary
BMT All Not mentioned Oral nonabsorbable
antibiotics
d
Sherertz et al., 1987 [35] Gainesville, FL Fungal infection All diseases that make
BMT necessary
BMT All 150 days None
Schmeiser et al., 1988 [30]
e
Ulm, Germany Death All diseases that make
BMT necessary
BMT All Not mentioned Total decontamination
Gamillscheg et al., 1991 [31] Graz, Austria Death Aplastic and sideroblastic
anemia; hematological
and solid malignancies
BMT All 10 months to 12 years Total decontamination
Withington et al., 1998 [36] Christchurch,
New Zealand
Fungal infection All diseases that make
BMT necessary
BMT and chemotherapy Patients from 2 of 3 study
periods
Not mentioned Prophylactic intranasal
amphotericin (selective)
Oren et al., 2001 [37] Haifa, Israel Fungal infection AML and ALL Chemotherapy Patients in 2 of 3 study arms
from 1 of 3 periods
Not mentioned None
NOTE. ALL, acute lymphatic leukemia; AML, acute myeloid leukemia; BMT, bone marrow transplantation.
a
For inclusion in the meta-analyses.
b
Patients were only randomized to be placed in a protected environment when a unit was available. If all units were occupied, patients were placed in hospital rooms with standard ventilation. Hence, this
study was counted as a nonrandomized controlled trial.
c
Some of the patients who were included in the study were not randomized.
d
Received only by patients in the intervention group.
e
The study is an interventional trial.
at::onJuly8,2013 http://jid.oxfordjournals.org/ Downloadedfrom
アウトカム RR
死亡リスク(RCTs) 0.86[0.65-1.14]
死亡リスク(non-RCTs) 0.87[0.60-1.25]
真菌感染症リスク(RCTs) 0.57[0.13-2.53]
真菌感染症リスク(non-RCTs) 0.29[0.15-0.54]
37. • Lymphomaに対するPEPAのstudyは,
(PEPA; protected environment-prophylactic Abx)
• N=58の小規模Studyのみ (Am J Med 1979; 66: 74 – 81.)
• CHOP-Bleoを行い, PEPA群 vs Controlに割り付け比較(RCT).
• 結果, Neutropeniaの頻度はPEPA群で有意に多い(255 vs 147d)が,
感染症合併率は2% vs 10%と有意にPEPA群で低いという結果.
ChemoのDoseもPEPA群で増量可能であったが,
寛解率は有意差なかった.
Journal of Antimicrobial Chemotherapy (2009) 63, Suppl. 1, i3–i13
