Immunostimulant for treatment of Malignant melanoma ?

A) Levamisol
B) BCG
C) Aldesleukin
D) Methotrexate


Ans: ?C (Aldesleukin)
Used as an adjunct in metastatic renal cell carcinoma, recently approved for Tx of metastatic melanoma.

Aldesleukin toxicity:

Treatment associated w/ serious cardiovascular toxicity resulting from capillary leak syndrome
involves loss of vascular tone, leakage of plasma proteins, adn fluid into extravascular space
may result in hypotension, reduced organ perfusion and even death.




A. Levamisole: 
Antiparasitic drug that stimulates maturation/ proliferation of T cells, enhances T- cell mediated immune responses.
Adjunctive treatment together w/ 5-FU and leucovorin after surgical resection in patients w/ dukes stage C colon cancer.
Has been used in treatment of nephrotic syndome.
Adverse effects: neutorpenia, anemia, thrombocytopenia, agranulocytosis, encephalopathy assoc. w/ demyelination.



B. BCG: 
Bacillus-calmette-guerin used as a non specific immunostimulant.
Used for intravesical therapy of bladder cancer.

D. Methotrexate 

It is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid.

Interferons beta 1a
Iinterferon beta 1b
Approved for use in MS



Interferons gamma B

Used in chronic granulomatous disease, activates phagocytes.


Oprelvekin:

Recombinant form of human IL 11 derived from genetically altered E. coli, stimulates platelet formation.
Used to treat thrombocytopenia.


Filgrastim:

Granulocyte colony stimulating factor- a 175 aminoacid glycoprotein produced by e. coli, stimulates CFU-G to increase neutrophil prodution. It is a recombinant, many valency, polypeptide. Lineage-specific hematopoietic agent, works on one cell line, stimulates peripehral blood stem cells.
Used to stimulate bone marrow recovery during cancer chemotherapy.


Sargramostim:

Derived from yeast, nonlineage specific hematopoetic agent as it stimulates both granulocytic and macrophage progenitor cells and the mature cells. Receptors on these cells to which sargramostim binds
similar to endogenous cytokine GM-CSF differing only in one amino acid.
Promotes myeloid recovery in patients given high dose chemotherapy for:

Non-hodgkins lymphoma
Acute lymphoblastic leukemia
Hodgkins disease patients who are undergoing bone marrow transplantation
Used to promote myeloid recovery after standard dose chemotherapy
Used to help myeloid recovery after BMT
To treat neutropenia associated w/ AIDS.

Dose related effects:

May be difficult to separate effects due to endogenous GM-CSF and exogenous Sargramostim.
High doses assoc. w/ bone pain, flu-like symptoms, fever, diarrhea, N and V, rash.
* contraindicated in patients w/ heart failure, pulmonary edema, and yeast hypersensitivity.






Epoetin- alpha (erythropoetin):
Recombinant human growth factor responsible for stimulating comitted erythroid precursors resulting in erythropoesis.

Recominent erythropoietin therapy in conjunction w/ adequate iron intake is used in the treatment w/ anemia assoc w/ :
Surgery
Treatment w/ zidovudine-induced anemia in AIDs patients
Cancer chemotherapy (myelosuppressive agents, when chemotherapeutic agents are highly nephrotoxic they may cause anemia)
Prematurity
Treatment w/ anemia assoc. w/ chronic renal disease including renal failure.



Thrombopoetin:

Myeloid cytokine growth factor is distinct from but analogous to erythropoietin, G-CSF and GM-CSF
cloning and expression of recombinant human thrombopoietin as a fusion protein combining GM-CSF and IL 3 has been very important for patients whose boen marrow has been compromised by chemo
selectively stimulates megakaryocytopoiesis.

Recombinant fusion protein-thrombopoetin + GM-CSF + IL 3 is used to treat anemia, neutropenia, and thrombocytopenia assoc. w/ high dose chemo.
Recombinant human thrombopoetin is used in accelerating platelet recovery in patients undergoing hematopoetic stem cell transplantation.