Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :267
Small font sizeDefault font sizeIncrease font size
Navigate here
  Search
 
  
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (237 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

 
  In this article
 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 » Conclusion
 »  References

 Article Access Statistics
    Viewed4001    
    Printed82    
    Emailed4    
    PDF Downloaded534    
    Comments [Add]    
    Cited by others 8    

Recommend this journal

 

  Table of Contents  
SYMPOSIUM FOR METRONOMICS AND ECONOMICS- CASE REPORT
Year : 2013  |  Volume : 50  |  Issue : 2  |  Page : 154-158
 

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review


1 Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Hemato Pathology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
3 Department of Cytogenetics, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
4 Department of Medical Oncology, L.H. Hiranandani Hospital, Powai, Mumbai, Maharashtra, India

Date of Web Publication27-Aug-2013

Correspondence Address:
S Banavali
Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.117033

Rights and Permissions

 » Abstract 

Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/refractory cancer. Here, we report a case of a 68-year-old gentleman having AML with high-risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high-dose (HD) cytosine arabinoside (Ara-C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low-intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.


Keywords: Elderly acute myeloid leukemia, metronomic therapy, metronomics, oral etoposide, oral 6TG


How to cite this article:
Tandon N, Banavali S, Menon H, Gujral S, Kadam P A, Bakshi A. Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review. Indian J Cancer 2013;50:154-8

How to cite this URL:
Tandon N, Banavali S, Menon H, Gujral S, Kadam P A, Bakshi A. Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review. Indian J Cancer [serial online] 2013 [cited 2020 Feb 18];50:154-8. Available from: http://www.indianjcancer.com/text.asp?2013/50/2/154/117033



 » Introduction Top


Acute myeloid leukemia (AML) is a disease of older adults with a median age of diagnosis of over 65 years. Advances in our understanding of the biology of the pathogenesis and prognosis of AML have not been matched with clinical improvements. AML in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. [1],[2] The prognosis of elderly AML patients remains poor despite recent therapeutic advances. [3] In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. [3],[4] The small percentage of patients who are cured and the high rate of treatment-related mortality in elderly patients with AML give rise to the question: Which patients would benefit from a primary curative approach, and which should be treated with a palliative approach? [5]

Based on the clinical and biological features, older AML patients are generally offered one of the four different treatment options: 'Standard' induction with infusional cytarabine and an anthracycline; 'low-intensity' induction with low-dose cytarabine, or more recently a hypomethylating agent like decitabine; 'supportive care' with hydrea, antibiotics, and transfusions; or enrollment on a 'clinical trial'. [4] Regardless of treatment, however, outcomes for older AML patients generally remain unsatisfactory. The wishes and expectations of the patient after thorough information about the risks and outlooks of the various therapeutic strategies ultimately guide the final therapy decisions in an individual patient. [3]

Over the last decade, metronomic chemotherapy - the chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule of administration, with no prolonged drug-free breaks - has emerged as a potential strategy to control advanced/refractory cancer disease. [6],[7] At the Tata Memorial Hospital, we have developed an oral metronomic protocol for the treatment of AML in children and young adults. [8],[9],[10] Here we report a case of a 68-year-old gentleman who achieved complete remission with this same protocol on an outpatient basis and was later treated with standard high-dose (HD) cytosine arabinoside (Ara-C) (HDAC) consolidation followed by metronomic maintenance. Appropriate literature justifying the use of low-dose oral therapies in the treatment of elderly AML patients has been reviewed. References for the review were identified through searches of Pubmed with the search terms 'acute myeloid leukemia' and 'elderly' alone or in combination in recent years. Articles were also identified through searches of files of the authors themselves. Only papers published in English were included. The final list was generated on the basis of originality and relevance to this review.


 » Case Report Top


A 68-year-old gentleman presented at our hospital on 21 June, 2010 with complaints of generalized weakness and dry cough of a duration of one and one-half months. Complete blood count (CBC) done outside was suggestive of 'myeloproliferative disorder' and thus he was referred to our hospital for further workup and treatment. The patient was a known case of hypertension not on any medication and was an old tobacco chewer, smoker, and an alcoholic.

On examination at our hospital, he had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1/4. There was no evidence of infection or bleeding from any site. He had pallor but no gum hypertrophy, lymphadenopathy, or organomegaly. His CBC revealed hemoglobin (Hb) of 10.1 g%, platelet count of 9.0 × 10 9 /L, and total leukocyte count of 8.0 × 10 9 /L with neutrophils (N): 24%, lymphocytes (L): 50%, monocytes (M): 25%, and myelocytes: 1%. The liver and renal function tests were essentially within normal range and lactate dehydrogenase (LDH) was marginally elevated at 232 U/L. The bone marrow examination showed 22% myeloperoxidase (MPO)-positive blasts which were positive for CD13 (CD: Cluster of differentiation), CD33, CD34, and human leukocyte antigen (HLA)-DR with a morphology similar to AML-M2 by the French-American-British (FAB) classification. The conventional katyotype analysis revealed that of 17 cells analyzed, four cells showed abnormal pseudodiploid karyotype pattern with clonal abnormalities of 5q deletion [(46 XY, del (5) (q15q21)] and 7q inversion [(46 XY, inv (7) (q11.2q q35)] in two cells each. The patient and his relatives were explained about the benefits and drawbacks of intensive standard induction chemotherapy versus oral metronomic low-intensity induction chemotherapy in view of age, comorbidities, and poor-risk cytogenetics. The patient opted for oral metronomic chemotherapy.

The patient was started on our institutional PrET (PrET: Prednisolone, etoposide, 6-thioguanine) chemotherapy. [8] He received oral prednisolone 30 mg twice a day (BD), etoposide (50 mg) 1 once a day (OD) and 1 BD every alternate days, and 6TG (40 mg) 1 q at bedtime (HS). This was given for 21 days every 28 days for two cycles, followed by another two cycles of just etoposide and 6TG. All chemotherapy was given on an outpatient basis and he did not require any admission during this period. The patient received five units of packed cells and six single-donor platelet transfusions during this period. The counts normalized by the end of the second cycle. The CBC in November 2010 showed Hb: 9.3, platelets: 110 × 10 9 /L, white blood cells (WBCs): 6.4 × 10 9 /L, absolute neutrophil count (ANC): 3.22 × 10 9 /L, and the bone marrow aspiration showed remission marrow with no excess of blasts.

As the patient had achieved morphological remission and had good performance status, he was given the option of continuing with oral palliative metronomic chemotherapy versus receiving standard high-dose cytarabine consolidation with the possibility of cure. The patient opted for the second option and he received two cycles of HDAC with 2 g/m 2 Ara-C every 12 hours on days 1, 3, and 5 (total 12 g/m 2 ) on 25 November 2010 and 03 January 2011. Overall, the patient tolerated HDAC well, though he required admission for febrile neutropenia during these cycles.

After completion of HDAC consolidation, he received oral metronomic maintenance therapy with etoposide 50 mg OD and 6TG 40 mg OD for 21 days every month along with sodium valproate 500 mg BD everyday for another six months. After completion of approximately one year of therapy, all treatment was stopped in July 2011. The off-treatment bone marrow evaluation done on 10 August 2011 showed no excess of blasts with a normal male diploid karyotype. Presently, he is on regular follow-up and his last CBC done on 04/06/2013 showed Hb: 14.8 g/dL, platelets: 294.0 × 10 9 /L, and WBC: 8.9 × 10 9 /L, with ANC of 5.60 × 10 9 /L.

Overall, the patient tolerated oral metronomic therapy well with no admission during this period and minimal monitoring with CBC and biochemical evaluation just once prior to each cycle. Very importantly, after completion of HDAC consolidation, the patient received the entire maintenance therapy at his hometown in rural India.


 » Discussion Top


Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly, [11] in whom there is no universally accepted standard of care as this patient population is clinically heterogeneous, and currently available therapies are largely ineffective. [4] Unsurprisingly, very few elderly AML patients have prolonged survival. [4] The United States Surveillance, Epidemiology and End Results (SEER) data from 2000 through 2007 showed that the median survival was two months for the untreated group versus six months for the treated group (P < 0.01). [12]

Elderly patients, defined in the literature as age > 60 years, historically have lower complete remission (CR) and relapse-free survival (RFS) rates than their younger counterparts. [5],[13] In a study of 211 patients by the South West Oncology Group, it was observed that there was a notably high frequency of secondary AML (24%), unfavorable cytogenetics (32%), multidrug resistance protein 1 (MDR1 protein) expression by leukemic blasts (71%), and functional drug efflux (58%) in elderly AML patients. [14] The Medical Research Council (MRC) AML8 trial, in which younger and older patients with AML received the same therapy, demonstrated a CR rate of 70% among individuals aged < 50, a CR rate of 52% for patients 60-69 years of age, and a dismal CR rate of 26% for individuals aged > 70. [15] Similar age-related differences were seen in the Cancer and Leukemia Group B (CALGB) 8525 trial, [16] in which individuals aged < 60 had a CR rate of 73% and four-year disease-free survival (DFS) rate of 31%, whereas patients who were aged > 60 had a CR rate of 47% and four-year DFS of 14%. Multiple novel agents like gemtuzumab ozogamicin (GO), multidrug resistance modulators, farnesyltransferase inhibitors, clofarabine, cloretazine, and FLT3 inhibitors have been tried alone or in combination with cytarabine, but none have showed to improve survival in this age group. [17],[18],[19],[20],[21] Also, the poor performance status and the presence of multiple comorbidities frequently preclude the use of intensive chemotherapy in patients aged > 60 years.

Achieving CR in leukemia is a requisite end point for prolonged survival, and the data from large population registries have validated the use of intensive induction approaches over less-intensive therapies in patients up to the age of 80 years. [22] For patients not fit for intensive treatment, intermediate intensity options are available. Low-dose cytarabine (20 mg subcutaneous BD for 10 days) repeated every four weeks was considered as a 'standard' nonintensive treatment for elderly AML patients. [23] However, with the availability of newer agents, things are changing. [24],[25] Also low-dose cytarabine was not found to be effective in patients with high-risk cytogenetics. [23]

Decision about fitness for treatment should not be made on the basis of age alone, but should arise from a comprehensive assessment of the patient as well as the biology of the disease. It has recently been discovered that patients with less proliferative AML (defined as a bone marrow blast percentage of 30% or less) stand to benefit from treatment with hypomethylating drugs such as 5-azacytidine and decitabine, which partially revert the aberrant methylation of cyctosine remnants in the DNA of leukemic cells. [26] Interestingly, patients with high-risk cytogenetic aberration also responded to hypomethylating agents. [27],[28]

There have been small single-center studies which have evaluated the use of low-dose chemotherapy regimens for elderly patients with AML. Herousseave and colleagues demonstrated a 40% CR rate using idarubicin alone and a similar CR rate using idarubicin in continuation with low-dose Ara-C. [29] Ruutu and colleagues observed a CR of 60% when using a combination of etoposide, idarubicin, and thioguanine. [30] In another study by Jackson et al., of 25 elderly AML patients not considered fit enough to tolerate intensive intravenous (IV) chemotherapy, who received a combination of oral etoposide and idarubicin, nine achieved CR. [31] Interestingly, autologous dendritic cells plus cytokine-induced killer cells were also shown to synergize with low-dose chemotherapy [response rate (RR) of 71.4 vs. 39.1% for controls]. [32]

In our elderly patient with comorbodities and high-risk cytogenetics, we gave oral metronomic induction because of the choice of the patient and based on our previous experience. [8],[9],[10] The combination of oral metronomic chemotherapeutic agents was not only well tolerated, but our patient also did not require any hospitalization during induction. Moreover, it was successful in achieving morphological and hematological CR. Angiogenesis seems to be important for both leukemogenesis and susceptibility to intensive chemotherapy, and antiangiogenic strategies are therefore now being considered for the treatment of AML. [33],[34],[35] Though recently other mechanisms of action have also been reported, metronomic therapies are believed to work primarily through antiangiogenic mechanisms. [6],[7] For the large group of elderly patients affected, intensive strategies are not possible because of high treatment-related mortality. In these patients, cytokine-directed antiangiogenic metronomic therapy maybe tried to increase the antileukemic effects of conventional intensive therapies. [33]

If only low-intensity treatment is given, then only a handful of patients would be long-term survivors. Buchner et al. have shown that postremission therapy is a prerequisite for long-term DFS. [36] Patients who do achieve a CR usually receive one to several cycles of consolidation therapy, often based on cytarabine in varying doses among different protocols, with older patients receiving fewer courses and lower doses in each course because of CNS toxicity. [3] Considering this, we offered our patient treatment with two courses of HDAC with an interval chance of achieving long-term DFS. The patient tolerated full doses of HDAC well with just one admission for febrile neutropenia in each cycle.

There is no adequate evidence for the use of maintenance treatment outside of clinical trials in AML. [37] Some patients do receive maintenance therapy post consolidation therapy, based on either chronic cytotoxic drugs or experimental drugs. Based on our past experience, [8],[9],[10],[38] we also gave our patient another six months of oral maintenance with etoposide and 6TG. Sodium valproate was added as an HDAC inhibitor in view of the upcoming data in AML patients and especially in view of high-risk cytogenetic features in our patient. [39],[40] Both valproic acid as well as 6TG have been shown to have antiangiogenic activity. [41],[42] The antiangiogenic activity of 6TG, together with its antimetabolite activity toward tumor cells, may contribute to its action during maintenance therapy in AML. [42] Our patient has been off treatment since 21 months and so far has an overall survival (OS) of 35 months and continues to be in complete hematological remission. Based on our previous data, Mukhopadhyay et al. also had treated 100 patients of AML > 50 years of age (median age: 65 years) with similar therapy. [43] In their series, 38% patients had a complete hematological response after six courses. The DFS and OS at 19 months of follow-up were reported at 18 and 32%, respectively.

This case report highlights that the combination of oral low-intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy maybe well tolerated by elderly patients especially with less proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. Thus, elderly patients even with comorbidities or even advanced-risk cytogenetics should not be left devoid of treatment.


 » Conclusion Top


Improving outcomes in older adults with AML remains a formidable challenge. There are limited treatment options and prognosis remains poor, thereby warranting the development of novel, less toxic treatment approaches with broader applicability. Combination of oral metronomic therapies and drug repositioning (e.g., sodium valproate as HDAC inhibitor)-an approach termed metronomics, [6] maybe especially of use in low-income and middle-income countries like India, where newer targeted agents (like azacytadine or GO) or low-intensity allotransplants are beyond the reach of most patients. Prospective, controlled studies are needed to support our findings.

 
 » References Top

1.Swords R and Santini V. In elderly patients with AML, which patients should be considered fit or unfit for standard induction therapy? Hematology Am Soc Hematol Educ Program 2012;2012:74-5.  Back to cited text no. 1
    
2.Yanada M, Naoe T. Acute Myeloid Leukemia in older adults. Int J Hematol 2012;96:186-93.  Back to cited text no. 2
[PUBMED]    
3.Krug U, Buchner T, Berdel WE, Muller-Tidow C. The treatment of elderly patients with Acute Myeloid Leukemia. Dtsch Arztebl Int 2011;108:863-70.  Back to cited text no. 3
    
4.Roboz GJ, Wissa U, Ritchie EK, Gergis U, Mayer S, Scandura JM, et al. Are low-intensity induction strategies better for older patients with acute myeloid leukemia? Leuk Res 2012;36:407-12.  Back to cited text no. 4
[PUBMED]    
5.Wedding U, Bokemeyer C, Meran JG. Working Group Geriatric Oncology of the German Society for Haematology and Oncology (DGHO); Austrian Society for Haematology and Oncology (OGHO); German Society for Geriatrics (DGG.) Elderly patients with acute myeloid leukaemia: characteristics in biology, patients and treatment. Recommendations of the Working Group Geriatric Oncology of the German Society for Haematology and Oncology (DGHO), the Austrian Society for Haematology and Oncology (OGHO) and the German Society for Geriatrics (DGG). Onkologie 2004;27:72-82.  Back to cited text no. 5
    
6.Pasquier E, Kavallaris M, André N. Metronomic chemotherapy: New rationale for new directions. Nature Rev Clin Oncol 2010;7:455-65.  Back to cited text no. 6
    
7.André N, Banavali S, Snihur Y, Pasquier E. Time for Metronomics in Developing Countries? Lancet Oncol 2013;14:e239-48.  Back to cited text no. 7
    
8.Banavali SD, Biswas G, Nair CN, Kurkure PA, Saikia TK, Parikh PM. PrET: An effective oral protocol for out-patient therapy in patients with acute myeloid leukemia. Ped Blood Cancer 2004;43:355.  Back to cited text no. 8
    
9.Banavali SD, Goyal L, Padhye B, Khadwal A, Nair CN, Gujral S, et al. A Novel Therapeutic Approach Yields Excellent Results in Minimally Differentiated Acute Myeloid Leukemia (AML-M0): Time to Think out of the box. Blood 2005;106:4615.  Back to cited text no. 9
    
10.Sengar M, Nair R, Banavali SD, Menon H. Metronomic approach for treatment of acute myeloid leukemia (AML): Dose intensity does not always matter. Haematologica 2009;94:551.  Back to cited text no. 10
    
11.Lin TL, Levy MY. Acute Myeloid Leukemia: Focus on novel therapeutic strategies. Clin Med Insights Oncol 2012;6:205-17.  Back to cited text no. 11
[PUBMED]    
12.Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: A population based study. Hematologica 2012;97:1916-24.  Back to cited text no. 12
    
13.Pinto A, Zagonel V, Ferrara F. Acute myeloid leukemia in the elderly: Biology and therapeutic strategies. Crit Rev Oncol Hematol 2001;39:275-87.  Back to cited text no. 13
[PUBMED]    
14.Leith CP, Kopecky KJ, Godwin J. Acute Myeloid Leukemia in the Elderly: Assessment of Multidrug Resistance (MDR1) and Cytogenetics distinguishes biologic subgroups with remarkably distinct responses to Standard Chemotherapy. A Southwest Oncology Group Study. Blood 1997;89:3323-9.  Back to cited text no. 14
    
15.Rees JK, Gray RG, Swirsky D, Hayhoe FG. Principal results of the Medical Research Council's 8 th acute myeloid leukemia trial. Lancet 1986;2:1236-41.  Back to cited text no. 15
[PUBMED]    
16.Löwenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, et al. On the value of intensive remission-induction chemotherapy in elderly patients of>65 years with acute myeloid leukemia: A randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group B. J Clin Oncol 1989;7:1268-74.  Back to cited text no. 16
    
17.Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 2005;104:1442-52.  Back to cited text no. 17
    
18.Daenen S, van der Holt B, Verhoef GE, Löwenberg B, Wijermans PW, Huijgens PC, et al. Addition of cyclosporin A to the combination of mitoxantrone and etoposide to overcome resistance to chemotherapy in refractory or relapsing acute myeloid leukemia: A randomized phase II trial from HOVON, the Dutch-Belgian Haemato-Oncology Working Group for adults. Leuk Res 2004;28:1057-67.  Back to cited text no. 18
    
19.List AF, Kopecky KJ, Willman CL, Head Dr, Persons DL, Slovak ML, et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: A Southwest Oncology Group study. Blood 2001;98:3212-20  Back to cited text no. 19
    
20.Lancet JE, Gojo I, Gotlib J, Feldman EJ, Greer J, Liesveld JL, et al. A phase 2 study of the farnesyl-transferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood 2007;109:1387-94.  Back to cited text no. 20
[PUBMED]    
21.Faderl S, Verstovsek S, Cortes J, Ravandi F, Beran M, Garcia-Manero G, et al. Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older. Blood 2006;108:45-51.  Back to cited text no. 21
[PUBMED]    
22.Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, et al. Age and acute myeloid leukemia: Real world data on decision to treat and outcomes from the Swedish acute leukemia registry. Blood 2009;113:4179-87.  Back to cited text no. 22
    
23.Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007;109:1114-24.  Back to cited text no. 23
[PUBMED]    
24.Pollyea DA, Zehnder J, Courte S, Gotlib J, Gallegos L, Abdel-Wahab O, et al. Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Hematologica 2013;98:591-6.  Back to cited text no. 24
    
25.Tavor S, Rahamim E, Sarid N, Rozovski U, Gibstein L, Aviv F, et al. High response rate for treatment with gemtuzumab ozogamicin and cytarabine in elderly patients with acute myeloid leukemia and favorable and intermediate-I cytogenetic risk. Clin Lymphoma Myeloma Leuk 2012;12:438-43.  Back to cited text no. 25
[PUBMED]    
26.Krug U, Lubbert M, Buchner T. Maintenance Stem Cell Transplantation in Acute Myeloid Leukemia revisited: Will new agents rekindle an old interest? Curr Opin Hematol 2010;17:85-90.  Back to cited text no. 26
    
27.Cashen AF, Schiller GJ, O'Donnell MR, DiPersio JF. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol 2010;28:556-61.  Back to cited text no. 27
[PUBMED]    
28.Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Gering U, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010;28:562-9.  Back to cited text no. 28
    
29.Harousseau JL, Rigal-Huguet F, Hurteloup P, Guy H, Milpied N, Ris J. Treatment of acute myeloid leukemia in elderly patients with oral idarubicin as a single agent. Eur J Haematol 1989;42:182-5.  Back to cited text no. 29
[PUBMED]    
30.Ruutu T, Elonen E. Etoposide, 6-thioguanine and idarubicin, an oral combination regimen (ETI) for the induction treatment of acute leukemia. Hematol Oncol 1991;9:87-92.  Back to cited text no. 30
[PUBMED]    
31.Jackson GH, Taylor PR, Iqbal A, Galloway MJ, Turner G, Haynes A, et al. The use of an all oral chemotherapy (idarubicin and etoposide) in the treatment of acute myeloid leukemia in the elderly: a report of toxicity and efficacy. Leukemia 1997;11:1193-6.  Back to cited text no. 31
[PUBMED]    
32.Dong M, Liang D, Li Y, Kong D, Kang P, Li K, et al. Autologous dendritic cells combined with cytokine-induced killer cells synergize low-dose chemotherapy in elderly patients with acute myeloid leukemia. J Intl Med Res 2012;40:1265-74.  Back to cited text no. 32
    
33.Padró T, Ruiz S, Bieker R, Bürger H, Steins M, Kienast J, et al. Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia. Blood. 2000;95:2637-44.  Back to cited text no. 33
    
34.Reikvam H, Hatfield KJ, Fredly H, Nepstad I, Mosevoll KA, Bruserud Ø. The angioregulatory cytokine network in human acute myeloid leukemia-from leukemogenesis via remission induction to stem cell transplantation. Eur Cytokine Netw 2012;23:140-53.  Back to cited text no. 34
    
35.Trujillo A, McGee C, Cogle CR. Angiogenesis in acute myeloid leukemia and opportunities for novel therapies. J Oncol 2012;2012:128608.  Back to cited text no. 35
[PUBMED]    
36.Büchner T, Urbanitz D, Hiddemann W, Rühl H, Ludwig WD, Fischer J, et al. Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia: Two multicenter studies of the German AML Cooperative Group. J Clin Oncol 1985:3:1583-90.  Back to cited text no. 36
    
37.Baer MR. Is there a role for maintenance therapy in acute myeloid leukemia? Best Pract Res Clin Haematol. 2009; 22: 517-21.  Back to cited text no. 37
    
38.Banavali SD, Singh R, Prasad M, Arora B, Nahar A, Vora T, et al. Amare-Kadam P. Is there a role for a novel maintenance therapy in pediatric patients with AML? Pediatric Blood Ca 2011; 57: 770 (abs PBO15)  Back to cited text no. 38
    
39.Kuendgen A, Bug G, Ottmann OG, Haase D, Schanz J, Hildebrandt B, et al. Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid. Clin Epigenetics. 2011; 2:389-99.  Back to cited text no. 39
    
40.Corsetti MT, Salvi F, Perticone S, Baraldi A, De Paoli L, Gatto S, et al. Hematologic improvement and response in elderly AML/RAEB patients treated with valproic acid and low-dose Ara-C. Leuk Res 2011;35:991-7.  Back to cited text no. 40
[PUBMED]    
41.Wang LH, Zhang ZH, Zhao L, Zhu CM, Zhao LS, Hao CL. Effect of Valproic Acid against Angiogenesis of Kasumi-1 Xenograft Tumor in Nude Mice. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2013;21:73-7.  Back to cited text no. 41
[PUBMED]    
42.Presta M, Belleri M, Vacca A, Ribatti D. Anti-angiogenic activity of the purine analog 6-thioguanine. Leukemia 2002;16:1490-9.  Back to cited text no. 42
[PUBMED]    
43.Mukhopadhyay S, Chitalkar P, Gupta P, et al. Oral chemotherapeutic agents in elderly acute myeloid leukemia patients, a study from a developing country. J Clin Oncol 2007; 25: 18S - Abs 7057.  Back to cited text no. 43
    



This article has been cited by
1 Metronomic therapy in pediatric oncology: A snapshot
Raja Pramanik,Sameer Bakhshi
Pediatric Blood & Cancer. 2019; 66(9): e27811
[Pubmed] | [DOI]
2 Treatment patterns and comparative analysis of non-intensive regimens in elderly acute myeloid leukemia patients—a real-world experience from India
Govind B. Kanakasetty,Chethan R,Lakshmaiah K C,Lokanatha Dasappa,Linu Abraham Jacob,Suresh Babu M C,Lokesh K N,Rudresha Antapura Haleshappa,Rajeev L K,Smitha Carol Saldanha,Koppaka Deepak,Patidar Rajesh,Vikas Asati
Annals of Hematology. 2019; 98(4): 881
[Pubmed] | [DOI]
3 Treatment of Langerhans cell histiocytosis with a modified risk-adapted protocol-experience from a tertiary cancer institute in India
Gaurav Narula,Nirmalaya D. Pradhan,Brijesh Arora,Sripad D. Banavali
Pediatric Blood & Cancer. 2018; 65(8): e27028
[Pubmed] | [DOI]
4 Potential role of metronomic chemotherapy in the treatment of esophageal and gastroesophageal cancer
Vanita Noronha,Vijay M. Patil,Amit Joshi,Anuradha Chougule,Shripad Banavali,Kumar Prabhash
Cancer Letters. 2017; 400: 267
[Pubmed] | [DOI]
5 Successful management of granulocytic sarcoma with concurrent hemophagocytic lympho histiocytosis in a child
Yogiraj Chopra,Mohammed Ramzan,Satya Prakash Yadav
Pediatric Hematology Oncology Journal. 2016; 1(3): 56
[Pubmed] | [DOI]
6 Metronomics in low and middle income countries: India showing the way!
N André,E Pasquier
Indian Journal of Cancer. 2013; 50(2): 112
[Pubmed] | [DOI]
7 Cytarabine
Reactions Weekly. 2013; 1482(1): 17
[Pubmed] | [DOI]
8 Metronomics in low and middle income countries: India showing the way!
Authors of Document André, N., Pasquier, E.
Indian Journal of Cancer. 2013;
[Pubmed]



 

Top
Print this article  Email this article
 

    

  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow