Even if Viagra is not needed, it is possible that the doctor will be able to determine the etiology of erectile dysfunction and prescribe appropriate treatmen https://vgraustralia.net it doesn't pay to forget about sexual activeness even at the first sings of malfunction.
Joitm.cbpt.cnki.net
Interpretations of Chemotherapeutic Protocols on SCLC
J Int Transl Med, 2014, 2(3):354-358; doi: 10.11910/2227-6394.2014.02.03.01
Open Access
Interpretations of Chemotherapeutic Protocols
on Small Cell Lung CancerFENG Ji-feng
Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu, 210000, China
Key words: Small Cell Lung Cancer; Diagnosis; Manifestations; Pathology; Staging; Prognostic factors; Chemotherapeutic protocols
Overview
Small cell lung cancer (SCLC) accounts for approximately present, only if patients are with the symptoms suggesting
14% of neuroendocrine tumors (about 20% of lung cancer)[1-2].
advanced disease can SCLC be diagnosed[6]. According to
It is reported that in United States only, about 31,000 patients Lung Screening Trial (NLST), annual and low-dose screening were confirmed with SCLC that are caused mainly by cigarette
with spiral CT scans could decrease the mortality induced by
smoking[2]. The incidence of SCLC in women is increasing and lung cancer in patients with asymptomatic high-risk, which male/female ratio is 1:1, though the general incidence has been could also be confirmed in NCCN Guidelines for Lung Cancer decreasing. The management of SCLC is described in the NCCN
Screening. But it is also believed that the CT scan is more
Guideline for Small Cell Lung Cancer.
effective in detecting non-small cell lung cancer (NSCLC) than detecting SCLC, which is predicated to be associated
SCLC is marked by early development of metastases, higher with the aggressiveness of SCLC, leading to the progression
growth fraction and fast doubling time, though it is very of symptomatic diseases between annual scans, subsequently
sensitive to radiotherapy or chemotherapy initially, most SCLC limiting the potential influences on cancer-specific mortality[6].
patients die eventually due to recurrent disease[4]. Some studies
indicated that compared with surgeries, radiotherapies and other
Manifestations
protocols, chemotherapy alone could prolong the survival time Patients with SCLC are always presented with symptoms
and relieve symptoms of most patients with extensive-stage of large mediastinal lymphadenopathy and hilar mass that
SCLC, but long-term survival time was rarely reported[5].
could cause dyspnea and cough and with those of metastatic diseases widely spread in human body like neurological
compromise, debility, weight loss and bone pain. However, a
The disease at early stage should be detected by a screening test solitary peripheral nodule without central adenopathy is not if it still can be cured. However, there is no effective screening unusually seen in SCLC patients, under which condition fine-test available to accurately detect SCLC at an early stage at needle aspiration alone could not completely distinguish small
Submit your manuscript [email protected] www.jitm.hk
J Int Transl Med, 2014, 2(3):354-358
cell carcinoma from large-cell or low- and intermediate-grade nodules, is defined as stage Ⅰ~Ⅲ that can be efectively treated neuroendocrine carcinoma [7-8].
by definitive radiotherapies, while the extensive-stage SCLC as stage Ⅳ or T3 ~ 4.
SCLC cells could produce polypeptide hormones consisting of adrenocorticotropic hormone and antidiuretic hormone Though the VA Lung Study Group also classifys SCLC into (ADH) that can cause Cushing syndrome and hyponatremia limited-stage and extensive-stage, the TNM is more useful for of malignancy such as syndrome of improper ADH secretion the selection of patients with T1-2, N0 disease in clinic, which (SIADH), respectively. The latter occurs more commonly should be used first for it is more precise in assessing the specific than the former in SCLC patients, whose treatment includes therapy and prognosis of SCLC in the future. demeclocycline, fluid restriction or vasopressin receptor inhibitor such as tolvaptan and conivaptin[9-10].
Complete staging data consist of physical and history examination, CT scans of adrenal glands, liver and chest, and
brain imaging by CT scan and MRI. However, if the patients
As a malignant epithelial tumor, SCLC consists of small cells is in extensive-stage, further staging is necessary except brain with finely granular nuclear chromatin, ill-defined cell borders,
imaging[11]. If in limited stage, PET-CT scan could be used to
inconspicuous or absent nucleoli and scant cytoplasm[7, 11], which
detect the distant metastses[12]. PET scan is more accurate in
is oval, spindle or round in shape, with high rate of mitotic staging patients with SCLC due to the highly metastatic property count. The SCLC can be sufficiently indentified by hematoxylin
of SCLC[15-17], and PET-CT is more superior than PET alone.
and eosin (HE) due to its distinctive and classic histology. Most Staging focuses not only on sites by laboratory tests or from of the small cell carcinoma, about 95%, originates from the lung,
symptomatic disease. If PECT-CT is not effective, bone marrow
but they can also arise from other parts besides pulmonary sites, with CT or MRI can be applied.
like genitourinary tract, gastrointestinal tract and nasopharynx,
etc., which have similar biological and clinical behaviors,
Prognostic factors
triggering a rate of extensive metastasis. Almost all patients with The most critical adverse prognostic factors include weight
SCLC have immunological responses to epithelial membrane loss, extensive-stage disease, markers related with excessive
antigen, thyroid transcription factor-1 and keratin, in which most bulk of disease and poor PS (3-4). As to patients with limited-
of them have positive responses to neuroendocrine differentiation stage disease, normal lactate dehydrogenase (LDH), female
markers consisting of neuron-specific enolase, synaptophysin, gender, stage Ⅰ disease and younger < 70 years are connected
neuron cell adhesion module and chromogranin A[7].
with favorable prognosis, whereas to those with extensive-stage disease, good PS, normal LDH and creatinine level, a single
metastatic site and younger age are most favorable prognostic
A combined approach is adopted by NCCN Panel to stage factors[18]. SCLC for the 2014 update, in which both the previous Veterans Administration scheme and ACJJ TNM system are used[11-
Indications of chemotherapy for
12]. Generally, ipsilateral supraclavcular and contralateral
SCLC[6]
mediastinal lymphadenopathy are classified as limited diseases
☆ Patients who are diagnosed with SCLC pathologically and
and about 2/3 patients have symptoms of overt hematogenous
metastases involving controlateral lung, brain, liver, bones,
☆ Karnofsky performance status (KPS) scores > 50 ~ 60
adrenal gland and/or bone marrow.
☆ Expected survival time ≥ 1 month;
In 2010, the International Association for the Study of Lung
☆ Ages ≤ 70 years.
Cnacer revised the TNM staging system for lung cancer, and the system is applicable to both SCLC and NSCLC, showing that the
Chemotherapy regiments for SCLC
various stage designations are of great prognostic significance in both cancers[13-14]. However, the limited-stage SCLC, includes Preferred single agentsT3 ~ 4 because of the over-large tumor volume or multiple lung
The preferred single agents for SCLC include paclitaxel,
Submit your manuscript [email protected] www.jitm.hk
J Int Transl Med, 2014, 2(3):354-358
docetaxel, topotecan, irinotecan, temozolomide, gemcitabine,
☆ Temozolomide 75 mg/m2/day ×21 days
ifosfamide (IFO), cyclophosphamide (CTX), vincristine (VCR),
carboplatin (CBP), adriamycin (ADM), cis-platinum (DDP),
vinorelbine (VLB) and etoposide (VP-16), etc.
☆ Relapse > 2 ~ 3 mo up to 6 mo:
☆ Topotecan PO or IV (category 1)
Preferred combination agents
Chemotherapeutic combination agents for SCLC consist of CAO
(ADM + CTX + VCR), VP (DDP + VP-16),CE (CBP + VP-
16), COME (CTX + VCR + MTX + VP-16), DAE (DDP
+ ADM + VP-16), VIP (IFO + VP-16 + DDP), cisplatin/
etoposide, carboplatin/etoposide and cisplatin/irinotecan, etc.
☆ Oral etoposide
☆ Temozolomide 75 mg/m2/day×21 days
Principles of chemotherapies for SCLC[19]
☆ Cyclophosphamide/doxorubicin/vincristine (CAV)
Chemotherapy as primary or adjuvant therapy
☆ Relapse > 6 mo: Original regimen
☆ Limited stage (maximum of 4 ~ 6 cycles):
☆ Cisplatin 80 mg/m2 day 1 and etoposide 100 mg/m2 days 1,
Interpretations of chemotherapeutic protocols for SCLC
Chemotherapy is the essential appropriate treatment for all
☆ Cisplatin 60 mg/m2 day 1 and etoposide 120 mg/m2 days 1,
patients with SCLC, while the adjuvant one is usually applied
to patients underwent surgical resections. As to patients with
☆ CBP AUC 5 ~ 6 day 1 and etoposide 120 mg/m2 days 1, 2,
limited-stage disease and good PS, chemotherapy concomitant
with concurrent thoracic radiotherapy is recommended[17].
☆ During chemotherapy + RT, cisplatin/etoposide is
However, chemotherapy alone could achieve favorable effect
recommended (category 1).
on patients with extensive-stage diseases, though radiotherapy
☆ The use of myeloid growth factors is not recommended
can also be used to alleviate patients' symptoms. In patients
during concurrent chemotherapy plus radiotherapy (category with extensive-stage disease accompanied with brain metastasis, 1 for GMCFS).
whether the patients have neurological symptoms or not decides
☆ Extensive stage (maximum of 4 ~ 6 cycles):
whether the chemotherapy is performed before or after whole-
☆ Cisplatin 80 mg/m2 day 1 and etoposide 80 mg/m2 days 1, 2,
brain radiotherapy[6].
☆ Cisplatin 75 mg/m2 day 1 and etoposide 100 mg/m2 days 1,
Both single and combination chemotherapy agents are proved
to be effective in SCLC[20]. EP is the most commonly used
☆ Cisplatin 25 mg/m2 days 1, 2, 3 and etoposide 100 mg/m2
combination agents that can replace anthracycline/alkylator-
based regimens because of its advantages in safety and efficacy
☆ CBP AUC 5 ~ 6 day 1 and etoposide 100 mg/m2 days 1, 2,
in limited-stage disease[21]. At present, EP combined with
concurrent thoracic radiotherapy is the most recommended
☆ Cisplatin 60 mg/m2 day 1 and irinotecan 60 mg/m2 days 1, 8,
therapy for patients with limited-stage disease[20]. However,
during the combination, EP is easily to cause pulmonary and
☆ Cisplatin 30 mg/m2 and irinotecan 65 mg/m2 days 1, 8
hematologic toxicity and esophagitis, but myeloid growth
☆ CBP AUC 5 day 1 and irinotecan 50 mg/m2 days 1, 8, 15
factors are not advisable in the concurrent chemoradiation[21]. In clinical practice, CBP, which is often used instead of cisplatin to
Subsequent chemotherapy
decrease the rates of nephropathy, neuropathy and emesis, can
☆ Relapse < 2 ~ 3 mo, PS 0 ~ 2
also cause higher rate of myelosuppression. In a meta-analysis
of 4 randomized trials, 663 SCLC patients were enrolled, which
concluded that the response rate (RR), overall survival (OS) and
☆ Topotecan PO or IV
progression-free survival (PFS) of patients receiving cisplation-
based versus CBP-based regimens were 67% vs. 66%, 9.6 vs.
Submit your manuscript [email protected] www.jitm.hk
J Int Transl Med, 2014, 2(3):354-358
9.4 months and 5.5 vs. 5.3 months, suggesting no significant 5 Demedts IK, Vermaelen KY, van Meerbeeck JP. Treatment differences between the two chemotherapeutic regimens[22].
of extensive-stage small cell lung carcinoma: current status and future prospects. Eur Respir J, 2010, 35(1): 202-15.
The combination agents also have been evaluated in SCLC 6 Cuffe S, Moua T, Summerfield R, et al. Characteristics patients in extensive stage, whose results give greater challenge
and outcomes of small cell lung cancer patients diagnosed
to EP in clinical efficacy, especially irinotecan concomitant with
during two lung cancer computed tomographic screening
platinum-based agents. A Japanese phase Ⅲ trial found that the
programs in heavy smokers. J Thorac Oncol, 2011, 6(4):
medium survival time and 2-year survival of patients treated
with irinotecan combined with cisplatin were 12.8 months 7 Travis WD. Advances in neuroendocrine lung tumors. Ann and 19.5%, evidently higher than the 9.4 months and 5.2% in
Oncol, 2010, 21(Suppl 7): vii65-71.
patients treated with EP[23]. However, another two phase Ⅲ trials
8 Renshaw AA, Haja J, Lozano RL, et al. Distinguishing
in United States showed no significant difference in RR and
carcinoid tumor from small cell lung carcinoma of the
OS between irinotecan combined with cisplatin and EP[24]. And
lung: correlating cytologic features and performance in
many other combination agents such as irinotecan plus CBP and,
the College of American Pathologists Non-Gynecologic
CBP plus oral etoposide, irinotecan plus platinum and etoposide
Cytology Program. Arch Pathol Lab Med, 2005, 129(5):
plus platinum were discovered to be effective in the treatment
SCLC. However, it was also reported that paclitaxel combined 9 Castillo JJ, Vincent M, Justice E. Diagnosis and with either CBP or cisplation plus etoposide achieved promising
management of hyponatremis in cancer patients. Oncologist,
results in a study, which could not improve patients' survival
2012, 17(6): 756-65.
time due to the unacceptable adverse responses[25]. Therefore, the
10 Verbalis JG, Zeltser D, Smith N, et al. Assessment of the
NCCN Panel finally regard platinum combined with etoposide
efficacy and safety of intravenous conivaptan in patients
as the standard combination agents for SCLC patients.
with euvolaemic hyponatraemia: subgroup analysis of a randomized, control study. Clin Endocrinol (Oxf), 2008,
In conclusion, many attempts have been made all over the world
to promote the long-term survival time of SCLC patients in both 11 Jett JR, Schild SE, Kesler KA, et al. Treatment of small cell limited and extensive stages by the complicated use of more
lung cancer: Diagnosis and management of lung cancer, 3rd
single or combination agents, or the utilization of dose-depended
ed: American College of Chest Physicians evidence-based
chemotherapy, non-cross-resistant chemotherapeutic regimens
clinical practice guidelines. Chest, 2013, 143: e400S-19S.
and maintenance therapies, however, which have failed to yield 12 Kalelerian GP, Gadgeel SM. Modern staging of small cell more significant advantages than the standard ones.
lung cancer. J Natl Canc Netw, 2013, 11(1): 99-104.
13 Lgnatius Ou SH, Zell JA. The applicability of the proposed
References
IASLC staging revisions to small cell lung cancer (SCLC)
1 Oberg K, Hellman P, Kwekkeboom D, et al. Neuroendocrine
with comparison to the current UICC 6th TNM Edition. J
bronchial and thymic tumours: ESMO Clinical Practice
Thorac Oncol, 2009, 4(3): 300-10.
Guidelines for diagnosis, treatment and follow-up. Ann 14 Goldstraw P, Crowley J, Chansky K, et al. The IASLC Oncol, 2010, 21(Suppl 5): v220-2.
Lung Cancer Staging Project: proposals for the TNM stage
2 Govindan R, Page N, Morgenszterm D, et al. Changing
groupings in the forthcoming (seventh) edition of the TNM
epidemiology of small-cell lung cancer in the United
Classification of malignant tumours. J Thorac Oncol, 2007,
States over the last 30 years: analysis of the surveillance,
epidemiologic, and end results database. J Clin Oncol, 15 Podoloff da, Ball DW, Ben-josef E, et al. NCCN task force: 2006, 24(28): 4539-44.
clinical utility of PET in a variety of tumor types. J Narl
3 Siegel R, Naishadham D, Jemal S, et al. Cancer statistics,
Compr Canc Netw, 2009, 7(Suppl 2): S1-26.
2013. CA Cancer J Clin, 2013, 63(1): 11-30.
16 Bradley JD, Dehdasgti F, Mintun MA, et al. Positron
4 Hann CL, Rudin CM. Management of small-cell lung
emission tomography in limited-stage small-cell lung
cancer: incremental changes but hope for the future.
cancer: a prospective study. J Clin Oncol, 2004, 22(16):
Oncology (Williston Park), 2008, 22(13): 1486-92.
Submit your manuscript [email protected] www.jitm.hk
J Int Transl Med, 2014, 2(3):354-358
17 Azad A, Chionh F, Scott AM, et al. High impact of 22 Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or
18F-FDG-PET on management and prognostic stratification
cisplatin-based chemotherapy in first-line treatment of
of newly diagnosed small cell lung cancer. Mol Imaging
small-cell lung cancer: the COCIS meta-analysis of
Biol, 2010, 12(4): 443-51.
individual patient data. J Clin Oncol, 2012, 30(14): 1692-8.
18 Foster NR, Mandrekar SJ, Schild SE et al. Prognostic 23 Noda K, Nishiwaki Y, Kawahala M, et al. Irinotecan
factors differ by tumor stage for small cell lung cancer: a
plus cisplatin compared with etoposide plus cisplatin for
pooled analysis of North Central Cancer Treatment Group
extensive small-cell lung cancer. N Endl J Med, 2002,
trails. Cancer, 2009, 115(12): 2721-31.
19 National Comprehensive Cancer Network. NCCN Clinical 24 Lara PN, Jr., Natale R, Crowley J, et al. Phase Ⅲ trial of
Practice Guidelines in Oncology for Small Cell Lung
irinotecan/cisplatin compared with etoposide/cisplatin
Cancer (Version 1.2015) [EB/OL]. Fort Washington: NCCN,
in extensive-stage small-cell lung cancer: clinical and
2015. Available at
pharmacogenomic results from SEOG S0124. J Clin Oncl,
2009, 27(15): 2530-5.
20 Spira A, Ettinger DS. Multidisciplinary management of 25 Niell HB, Herndon JE 2ed, Miller AA, et al. Randomized
lung cancer. N Engl J Med, 2004, 350(4): 379-92.
phase Ⅲ intergroup trial of etoposide and cisplatin with
21 Sundstrom S, Bremnes RM, Kaasa S, et al. Cisplatin
or without paclitaxel and granulocyte colony-stimulating
and etoposide regimen is superior to cyclophosphamide,
factor in patients with extensive-stage small-cell lung
epirubicin, and vincristine regimen in small-cell lung
cancer: Cancer and Leukemia Group B Trial 9732. J Clin
cancer: results from a randomized phase III trial with 5
Oncol, 2005, 23(16): 3752-9.
years' follow-up. J Clin Oncol, 2002, 20(24): 4665-72.
Submit your manuscript [email protected] www.jitm.hk
Source: http://joitm.cbpt.cnki.net/WKC/WebPublication/wkDownLoad.aspx?fileID=4d9137ce-c472-42f0-8689-b63a7def036e
European Heart Journal (2013) 34, 1708–1715 Expert position paper on the use of proton pumpinhibitors in patients with cardiovascular diseaseand antithrombotic therapy Stefan Agewall1*, M. Cattaneo2, J.P. Collet3, F. Andreotti4, G.Y.H. Lip5,F.W.A. Verheugt6, K. Huber7, E.L. Grove8, J. Morais9, S. Husted10, S. Wassmann11,G. Rosano12, D. Atar1, A. Pathak13, K. Kjeldsen14, and R.F. Storey15, on behalf of ESCWorking Group on Cardiovascular Pharmacology and Drug Therapy and ESC
Tohoku J. Exp. Med., 2006, 209,B e 2 a0l Effects of Fluvastatin in Rats Fluvastatin Alters Psychomotor Performance and Daily Activity but not the Spatial Memory in Rats SUKRUCAN H. BAYTAN, MEHMET ALKANAT, MEHMET OZEREN,1 MURAT EKINCI2 and AHMET AKGUNDepartment of Physiology, 1Department of Obstetrics and Gynecology, Karadeniz Technical University, Medical School, Trabzon, Turkey, and