Difference between revisions of "Alvocidib (Flavopiridol)"

Revision as of 02:06, 11 August 2023

Mechanism of action

From the NCI Drug Dictionary: A synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis.
Route: PO

Preliminary data

Acute myeloid leukemia

FLAM

FLAM: FLavopiridol (Alvocidib), Ara-C (Cytarabine), Mitoxantrone

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Zeidner et al. 2015 (JHOC-J1101)	Randomized Phase 2 (E)	7+3d, high-dose dauno	Superior CR rate

Chemotherapy

Alvocidib (Flavopiridol) 50 mg/m² IV once per day on days 1 to 3
Cytarabine (Ara-C) 667 mg/m²/day IV continuous infusion on days 6 to 8 (total dose: 2000 mg/m²)
Mitoxantrone (Novantrone) 40 mg/m² IV once on day 9

One course

References

JHOC-J1101: Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. link to original article contains dosing details in manuscript link to PMC article PubMed

Chronic lymphocytic leukemia

Also known as

Generic name: flavopiridol
Code names: HMR-1275, L-868275

@@ Line 1: / Line 1: @@
 ==Mechanism of action==
-Flavonoid alkaloid CDK9 kinase inhibitor
+From the [https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=42068 NCI Drug Dictionary]: A synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis.
 <br>Route: PO
-==Diseases for which it is used==
+==Preliminary data==
-*[[Acute myeloid leukemia]]
+===[[Acute myeloid leukemia]]===
-*[[Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL)]]
+==FLAM {{#subobject:8a86fb|Regimen=1}}==
-==History of changes in FDA indication==
+FLAM: '''<u>FL</u>'''avopiridol (Alvocidib), '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''itoxantrone
-*4/13/2007: Granted orphan status for treatment of [[Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL) | B-cell chronic lymphocytic leukemia (B-CLL)]] or prolymphocytic leukemia arising from CLL.
+===Regimen {{#subobject:5340f1|Variant=1}}===
-*4/23/2014: Granted orphan designation for the treatment of patients with [[Acute myeloid leukemia | acute myeloid leukemia (AML)]]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|Comparator
+!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ Zeidner et al. 2015 (JHOC-J1101)]
+| style="background-color:#1a9851" |Randomized Phase 2 (E)
+|[[#Cytarabine_.26_Daunorubicin|7+3d, high-dose dauno]]
+| style="background-color:#1a9850" |Superior CR rate
+|-
+|}
+====Chemotherapy====
+*[[Alvocidib (Flavopiridol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Cytarabine (Ara-C)]] 667 mg/m<sup>2</sup>/day IV continuous infusion on days 6 to 8 (total dose: 2000 mg/m<sup>2</sup>)
+*[[Mitoxantrone (Novantrone)]] 40 mg/m<sup>2</sup> IV once on day 9
-[[Category:Drug index]]
+'''One course'''
-[[Category:Chemotherapy]]
+===References===
+# '''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709/ PubMed]
+===[[Chronic lymphocytic leukemia]]===
+==Also known as==
+*'''Generic name:''' flavopiridol
+*'''Code names:''' HMR-1275, L-868275
+[[Category:Drugs]]
 [[Category:Oral medications]]
-[[Category:Kinase inhibitors]]
 [[Category:CDK inhibitors]]
-[[Category:Acute myeloid leukemia medications]]
+[[Category:Acute myeloid leukemia medications (investigational)]]
-[[Category:Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL) medications]]
+[[Category:Chronic lymphocytic leukemia medications (investigational)]]
+[[Category:Investigational drugs]]
-[[Category:Drugs FDA approved in 2007]]
-[[Category:Orphan drug]]