Jan 03, 2016
THERAPEUTIC MODALITIESTHERAPEUTIC MODALITIES
LOCAL TREATMENTSSURGERYRADIATION THERAPY
SYSTEMIC TREATMENTSCHEMOTHERAPYBIOLOGIC THERAPY
OUTLINEOUTLINE
I. The Cell Cycle
II. Categories of Drugs
III. Biologic Characteristics of Cancer Cells
IV. Mechanisms of Drug Resistance
V. Clinical Uses of Cytotoxic Agents
VI. Timing and Response to Chemotherapy
VII.Chemotherapeutic Agents
PHASESSTATE PHASE DESCRIPTION
Quiescent/ senescent
Gap 0 (G0) Resting phase; the cell left the cycle;Stopped dividing.
Interphase Gap 1 (G1) Cells increase in size G1 checkpoint control mechanism ensures everything ready for DNA synthesis.
Synthesis (S) DNA replication occurs.
Gap 2 (G2) The cell continues to grow. G2 checkpoint control mechanism ensures everything ready to enter the M phase and divide.
Cell Division Mitosis (M) Cell growth stops,cellular energy focused on the orderly division into two daughter cells. Metaphase Checkpoint ensures the cell ready to complete cell division.
Categories of Drugs
1. Phase nonspecific
a. Cycle-nonspecific drugs - nondividing cells (steroid hormones, antitumor antibiotics except bleomycin).
b. Cycle-specific, phase-nonspecific drugs – effective if cells proceed through the cycle
can inflict injury at any point in the cycle (alkylating agents).
Phase Nonspecific Drugs Pharmacokinetics
• Linear dose–response curve: the greater the amount of drug administered, the greater the fraction of cells killed.
Log-cell number(response)
dose
Categories of Drugs
2.Phase specific
Cycle-specific, phase-specific drugs are effective only if present during a particular phase of the cell cycle.
Cell Cycle & Phase Specific Drugs
G0 phase: glucocorticoids for mature lymphocytes
G1 phase: L-Asparaginase
S phase: procarbazine and antimetabolites
G2 phase: bleomycin and plant alkaloids
M phase: plant alkaloids
Phase Specific Drugs Pharmacokinetics
• Phase-specific drugs reach a limit in cell-killing ability, but its effect is a function of both time and concentration. (maintaining a drug conc’n over a period of time, more cells enter specific lethal phase of the cycle and killed.
Log-cell number
dosage
Biologic Characteristics of Cancer Cells and Possible use of Chemotherapy
Biologic characteristics of cancer cells can be exploited to make them susceptible to drugs.
Although malignant cellular proliferation occur in absence of normal growth controls, cancer cells depend on same mechanisms for cell division found in normal cells.
Damage to those mechanisms leads to cell death in both normal and malignant tissues.
Biologic Characteristics of Cancer Cells and Possible use of Chemotherapy• Exploitation of apoptosis in cancer (Radiation
and most cytotoxic agents kill cancer cells by damaging cell and inducing apoptosis.)
• Exploitation of proliferation control factors in cancer. (Biologic response modifiers stimulate selected immune cells, which then demonstrate anticancer activity [interferons, ILs, and GFs.]
• Exploitation of maturation abnormalities. Maturation factors (Transretinoic acid, Vit. D,
Cytosine arabinoside)/ Eradication of stem cells leaving behind a pop’n of maturing cells.
Biologic Characteristics of Cancer Cells and Possible use of Chemotherapy• Angiogenesis inhibition: exploitation of
dependence of cancer cells to induce the formation of their own blood supply to proliferate. Angiogenesis inhibition is being actively pursued as a tool for cancer treatment.
Mechanisms of drug resistance• Tumor cell heterogeneity
• Spontaneous genetic mutations/ drug-resistant
• Goldie-Coldman hypothesis indicates that probability of a tumor population containing resistant cells is a fxn of total # of cells present.
• Single-drug resistance (Catabolic enzymes, transport proteins.
• Multidrug resistance. (P-170 and the mdr-1 gene, loss of apoptosis)
Indications for use of Chemotherapy• To cure certain malignancies • To palliate symptoms in pxs with disseminated
cancer when potential benefits of treatment exceed side effects
• To treat asymptomatic pxs in ff circumstances:
a. When cancer is aggressive and treatable (e.g., acute leukemia, small cell lung cancer)
b. When treatment proven to decrease rate of relapse and increase disease-free interval or increase absolute survival (colon CA, stages I or II breast CA, Osteogenic sarcoma)
Contraindications for use of Chemotherapy1. Inadequate facilities to evaluate px’s response
to therapy & to monitor & manage toxic rxns
2. When px not likely to survive longer even if tumor shrinkage could be accomplished
3. When the px not likely to survive long enough to obtain benefits (severely debilitated patients)
4. When patient is asymptomatic with slow-growing, incurable tumors, in which case chemotherapy should be postponed until symptoms require palliation
Timing of ChemotherapyA) Induction chemotherapy (initial therapy to
achieve significant cytoreduction (complete remission) of disease.
B)Consolidation/Intensification chemotherapy (postremission, same drugs used in induction (consolidation) or non-cross resistant drugs (intensification) are repeated. (to prolong remission and overall survival eg. in ALL, AML).
C)Adjuvant chemotherapy After local treatment (surgical or radiation), adjuvant used to prevent local or distant relapse.
Timing of ChemotherapyD) Neoadjuvant chemotherapy. Before local
therapy, neoadjuvant chemotherapy is given in hopes of reducing extent of local treatment or increasing its effectiveness.
E) Maintenance chemotherapy. Prolonged, low-dose outpatient chemotherapy intended to prolong duration of remission and achieve cure in patients in remission.
F) Salvage chemotherapy After failure of other treatments (surgery, radiation, or prior chemo), used to control disease or provide palliation.
Response to Chemotherapy• Induction Therapy:• Complete response (CR) - disappearance of dx on
imaging for at least 1 mo. eg in AML, CR defined as <5% blasts in BM, no circulating blasts in blood & no extramedullary dx by day 14 after induction.
• Partial response (PR) - decrease of 50% or more in sum of products of biperpendicular diameters; no new sites of dx at least 1 month.
• Stable disease in pxs with <50% response without actual progression of disease.
• Progression 25% inc in sum of products of biperpendicular diameters of known lesions or any new sites of disease.
Response to Chemotherapy• Adjuvant chemotherapy:
• Relapse-free survival measures time from start of tx to regrowth of tumor to detectable levels.
• Salvage chemotherapy:
• Progression-free survival remains major end point in patients with advanced disease and equivalent of relapse-free survival in adjuvant setting.
Classification of Chemotherapy Drugs
• CELL-CYCLE SPECIFIC DRUGS
• Antimetabolites• Mitotic Inhibitors (Vinca
Alkaloids, Epipodophyllotoxins, Taxanes)
• Camptothecins
• CELL-CYCLE NONSPECIFIC DRUGS
• Alkylating agents• Antitumor antibiotics• Hormones• Hormone Antagonists• Miscellaneous Agents
Cell Cycle-Specific Agents
• Administered in divided doses or as a continuous infusion which facilitates lysis of cells in certain phases of the cycle.
• Reduce growth fraction (# of cells present in the cycle) of the tumor.
Antimetabolites• Structural analogues of normal molecules
essential for cell growth and replication.
• inhibit enzymes necessary for synthesis.
• major effect - interfering with building blocks of DNA synthesis
• activity greatest in S phase of cell cycle
• most effective when cell proliferation is rapid.
• Nonlinear dose-response curve (except FU). • eg (Capecitabine, 5-FU, Cytosine arabinoside,
Gemcitabine, Deoxycoformycin, 6-Mercaptopurine, Floxuridine, Methotrexate, Fludarabine, Thioguanine
Methotrexate (amethopterin, MTX)I: A wide variety of conditions
MOA: Folic acid antimetabolite.
• blocks dihydrofolate reductase, preventing formation of
reduced tetrahydrofolic acid; block formation of thymidylate
from deoxyuridylate & prevents synthesis of DNA;
• also inhibits RNA and protein synthesis
• prevents cells from entering S phase.
Metab: min metabolized; excreted in urine unchanged (90%)
Toxicity (reversed with Leucovorin 1:1)
• Dose limiting. Myelosuppression, stomatitis, renal dysfxn
• High-dose regimens. N/V, RT necrosis, cortical blindness
Dose: 2.5-mg tablets and 20 to 1000-mg vials.
Modification. must not be given to px w/ CrCl <60mL/min
Mercaptopurine (6-MP, Purinethol) I: ALL (maintenance therapy)
MOA: Purine antimetabolite.
• Undergoes extensive metabolic changes; complex
• Inhibits de novo purine synthesis, purine interconversion
• Competes with ribotides for enzymes responsible for conversion of inosinic acid to adenine and xanthine ribotides.
Metab: slowly degraded in liver, largely by xanthine oxidase.
Toxicity
• Dose limiting. Myelosuppression
• Common. N/V, anorexia (25%); reversible cholestasis
Dose: Supplied as 50-mg tablets, 70 to 100mg/m2
Modification. Reduced by 50-75% for pxs w/ hepatic dysfxn.
Fluorouracil (5-FU, Adrucil) I: A wide variety of carcinomas
MOA: Pyrimidine Antimetabolite
• Interferes with DNA synthesis by blocking thymidylate
synthetase, (conversion of deoxyuridylic acid to thymidylic a)
• Incorporated into several RNA species, interfere with RNA fxn and protein synthesis.
• S-phase specific but acts in other cell cycle phases
• Unique in having a log linear cell-killing action.
Metab: hepatic; 90% excreted in urine, bile & breath (CO2).
Toxicity: Dose limiting Myelosuppression, mucositis/diarrhea
• Common: Nasal discharge; eye irritation and lacrimation
Dose: 500-mg vials
Modification: w/held if px has diarrhea, infection, leukopenia,
Leucovorin (citrovorum factor, folinic acid, 5-formyl tetra-hydrofolate)
I: Combined w/ 5-FU in tx of colorectal & other adenoCAs; rescue agent for antifol toxicity (MTX)
MOA: a tetrahydrofolic acid derivative that acts as a cofactor
for carbon transfer rxns in synthesis of purines & pyrimidines
• Inhibits effects of MTX & other DHFR antagonists.
Metabolism. Excreted in the urine as metabolites
Toxicity. Potentiates toxic effects of fluoropyrimidine therapy
Dose: 50-, 100-, and 350-mg vials for IV use and as a 60-mg bottle for oral use
Mitotic Inhibitors
• Mitotic inhibitors interfere with formation of mitotic spindle, causing metaphase arrest.
• M-phase active, but they may also have activity in G2 and S.
• Include the vinca alkaloids, the epipodophyllo-toxins, and the taxanes.
Vinca Alkaloids• A.k.a plant alkaloids - extracts of periwinkle
plant.
• bind to microtubular proteins, essential in forming mitotic spindle of the dividing cells. This binding arrests mitosis, which eventually causes cell death.
• act mainly in M phase; however, high doses can also disrupt RNA and protein synthesis.
• Vinblastine, Vincristine, Vindesine, Vinorelbine
Vinblastine (Velban) I: Lymphomas, testicular carcinoma
MOA: Binds to microtubular proteins. • Inhibits RNA synthesis by affecting DNA-dependent
RNA polymerases. • Cell cycle–phase specific; • arrests cells at the G2-phase and M-phase interface.
Metab: mainly hepatic, minimal renal
Toxicity: Dose-limiting Neutropenia • Common Cramps or severe jaw, back pain
Dose: 10-mg vials
Dose modification. Decrease dose by 50% for patients with serum bilirubin greater than 3.0 mg/dL.
Vincristine (Oncovin/Vincasar/leurocristine) I: A wide variety of malignancies
MOA: Same as vinblastine
Metabolism. Same as vinblastine
Toxicity Dose-limiting. Severe paresthesias, ataxia, Foot
drop (slapping gait), muscle wasting, cranial nerve palsies,
paralytic ileus, obstipation, abdominal pain, cortical
blindness, seizures
• Common. Tissue necrosis, alopecia (20% to 40%)
Dose: 1 mg/mL vials
Modification. Hepatic dysfunction; same as for vinblastine
Epipodophyllotoxins
• isolated from the mandrake plant (May crab apple).
• act in the premitotic phase, G2 and S, and interfere with topoisomerase II enzyme reaction.
• Inhibition of topoisomerase interferes with transcription and replication by causing DNA damage, inhibition of DNA replication, failure to repair strand breaks, and then, cell death.
• Etoposide, Teniposide
Etoposide (VP-16, VePesid)I: Testicular CA, Lung CA, lymphoma, & other malignancies
MOA: An epipodophyllotoxin;
• a topoisomerase II inhibitor
• cell cycle–phase specific at G2, late S, and M phases.
Metab: Highly bound to plasma proteins; metabolized by the
liver. Excreted in urine (40%) intact & degraded drug;
excretion of remaining 60% is uncertain.
Toxicity Dose-limiting: Neutropenia
• Common. N/V (w/ oral dosing); mild alopecia ; hypotension if rapidly infused
Dose: 50 mg/m2 PO daily for 21 days/ 50 to 120 mg/m2 IV daily for 3 to 5 days
DI. CCBs, methotrexate may increase cytotoxicity
Taxanes
• Taxanes cause mitotic arrest by forming abnormal spindle fibers and mitotic asters.
• Taxanes not only bind to microtubules but also promote microtubule assembly and resistance to depolymerization, resulting in production of nonfunctional microtubules.
• Docetaxel, Paclitaxel
Paclitaxel (Taxol) I: Breast, ovarian CA, AIDS-assoc Kaposi’s sarcoma, others
MOA: Taxane; bind to microtubules and promote
microtubule assembly & resistance to depolymerization,
resulting in production of nonfunctional microtubules. Metab: Nearly totally protein bound & distributed well to
body fluids (effusions) w/ a plasma half-life of about 5 hours
Toxicity Dose-limiting: Neutropenia, prev. treated w/ cisplatin
• Hypersensitivity, Peripheral neuropathy.
Common: Alopecia, thrombocytopenia; transient arthralgias
& myalgias w/in 3 days of tx (ameliorated by NSAIDs), brady
Dose: 30-, 100-, and 300-mg vials/ 135 to 175mg/m2
Dose modification. Hematologic
Camptothecins• Name derived from the Chinese tree
Camptotheca acuminata
• new subcategory of cell cycle–specific drugs.
• act in S phase and inhibit topoisomerase I, a nuclear enzyme necessary for maintaining DNA structure, resulting in single-stranded DNA breaks and subsequently cell death.
• Irinotecan, Topotecan
Irinotecan (Camptosar, CPT-11)
I: Colorectal CA refractory to 5-FU–based chemotherapy
MOA: water-soluble analogue of camptothecin, relatively inactive prodrug, converted to active agent
• Inhibits topoisomerase I
• cell cycle– phase specific.
Metab. Metabolized in liver. Renal clearance.
Toxicity Dose-limiting. Profuse diarrhea
• Common. Neutropenia; mild N/V, abdominal cramps; flushing during administration; alopecia
Dose: 100-mg vials/ 125mg/m2
Dose modification. Use with caution for hepatic insufficiency.
Cycle-Nonspecific Drugs• Effective through all phases of cell cycle
• Directly affect DNA molecule and display no specificity for cells that are dividing.
• More toxic than cycle–specific drugs (does not differentiate between normal & malignant cells.
• Given in bolus doses because they cause death independently of the proliferative state of cell.
• Reduce the number of cells that make up a tumor, which is known as the tumor burden.
Alkylating Agents• target DNA, cytotoxic, mutagenic & carcinogenic. All
produce alkylation through the formation of intermediates.
• Impair cell fxn by transferring alkyl groups to amino,
carboxyl, sulfhydryl, or phosphate groups of important mol.
• nucleic acids & proteins alkylated. (N-7) position of
guanine in DNA & RNA - most actively alkylated site; O-6
grp of guanine alkylated by nitrosoureas.
• Alkylation of guanine results in abnormal nucleotide
sequences, miscoding of messenger RNA, cross-linked
DNA strands that cannot replicate, breakage of strands, and
other damage to transcription & translation of genetic mat’l.
• Primary mode of action: cross-linking of DNA strands.
Alkylating AgentsMustard gas derivatives: Mechlorethamine,
Cyclophosphamide, Chlorambucil, Melphalan,& Ifosfamide.
Ethylenimines: Thiotepa & Hexamethylmelamine.
Alkylsulfonates: Busulfan.
Hydrazines and Triazines: Altretamine, Procarbazine,
Dacarbazine and Temozolomide.
Nitrosureas: Carmustine, Lomustine and Streptozocin
(unique, can cross BBB).
Metal salts: Carboplatin, Cisplatin, and Oxaliplatin.
Cyclophosphamide (Cytoxan)I: Used in a wide variety of conditions
MOA: Alkylation, also inhibits DNA synthesis
Metab: requires activation by liver microsomal oxidase
system to form an aldehyde that decomposes in plasma and
peripheral tissues to yield acrolein & an alkylating metabolite
(phosphoramide mustard); excreted in urine.
Toxicity: Dose limiting: Myelosuppression, hemorrhagic
Cystitis
• Common. Alopecia, stomatitis, aspermia, amenorrhea; headache (fast onset, short duration), N/V.
Dose: 25 or 50mg tabs; vials contain 100 to 1000 mg
Dose modification. Hematologic; may be required for hepatic functional impairment
Busulfan (Myleran)I: CML, bone marrow transplantation (high doses)
MOA: Alkylation
Metabolism: Acts directly; catabolized to inactive products excreted in the urine.
Toxicity Dose limiting. Reversible and irreversible myelosuppression with slow recovery; blood cell counts fall for about 2 weeks after discontinuation of drug.
• Common. GI upset (mild), sterility
Dose: 2-mg tablets/ 2-8mg/day PO
Dose modification. Hematologic
Procarbazine (Matulane, Natulan, N-methylhydrazine)I: Hodgkin & Non-Hodgkin Lymphoma, Myeloma, Brain Ca
MOA: DNA alkylation and depolymerization; Methylation of
nucleic acids; Inhibition of DNA, RNA, and protein synthesis
Metab: Metabolic activation required. Readily enters CSF. Degraded in liver to inactive cmpds, excreted in urine
Toxicity: Dose limiting. Myelosuppression, which may not begin until several weeks after starting treatment
• Common. N/V, which decreases w/ continued use; myalgia, arthralgia; sensitizes tissues to radiation
Dose: 50-mg capsules
Modification Reduce dose in pxs w/ hepatic, renal, or bone marrow dysfunction.
Streptozocin (streptozotocin, Zanosar)I: Islet cell CA (w/ FU), carcinoid syndrome
MOA: Alkylation; Inhibits DNA synthesis & DNA repair
enzyme, guanine-O6-methyl transferase; affects pyrimidine
nucleotide metab, inhibits enzymes in gluconeogenesis
Metab: extensively metabolized, a short plasma half-life;
Crosses BBB; Excreted in urine.
Toxicity Dose limiting: Nephrotoxicity
• Common: N/V, myelosuppression, hypoglycemia, vein irritation
Dose: 1-g vials/ 1.0 g/m2 IV weekly, or 0.5 g/m2 IV daily
Modification. Proteinuria or elevated serum creatinine levels
Cisplatin (cis-diaminedichloroplatinum [CDDP], Platinol)
I: A wide variety of malignancies
MOA: heavy metal alkylator of DNA; Covalently bonds to
proteins, RNA, & esp DNA, forming DNA cross-linking &
intrastrand N-7 adducts.
Metab: Widely distributed in body, except for CNS. Long
half-life in plasma (3 days); drug (30%) & metabolites
excreted in urine; biliary excretion <10%
Toxicity Dose limiting: Cumulative renal insufficiency/ Peripheral sensory neuropathy, Ototoxicity with tinnitus
• Common: Severe N/V, hypokalemia, hypomagnesemia & mild myelosuppressiona.
Dose: 10- and 50-mg vials/ 40 to 120mg
Mod: Renal fxn must return to normal before cisplatin given
Antitumor Antibiotics• Isolated from fermented broths ofStreptomyces • Focal point of cytotoxicity is the DNA. • Interfere w/ DNA-directed RNA synthesis by
intercalating between base pairs of DNA and
generating toxic oxygen-free radicals, causing
single- or double-stranded DNA breaks. • cycle–nonspecific, useful in slow-growing
tumors with low growth fractions. • Anthracyclines: Doxorubicin, Daunorubicin, Epirubicin,
Mitoxantrone, and Idarubicin.
• Chromomycins: Dactinomycin and Plicamycin.
• Miscellaneous: Mitomycin and Bleomycin.
Actinomycin D (dactinomycin, Cosmegen)I: Trophoblastic neoplasms, sarcomas, testicular CA, Wilms’
MOA: Intercalates between DNA base pairs & prevents
synthesis of mRNA; inhibits topoisomerase II
Metab: Unknown; extensively bound to tissues, resulting in
long half-life in plasma & tissue, Excreted in bile and urine
Toxicity Dose limiting. Myelosuppression
• Common. N/V (worsening after successive daily doses);
alopecia, acne, erythema, desquamation,hyperpigmentation;
radiation-recall rxn; a vesicant that causes necrosis
Dose: 0.5-mg vials/ 0.25 to 0.60 mg/m2 IV daily for 5 days
Modification. Reduce by 50% in of renal or hepatic dysfxn.
Bleomycin (Blenoxane)I: Lymphoma, SCC, testicular Ca, malignant effusions others
MOA: Binds to DNA, inhibiting synthesis of DNA, RNA and
Proteins; Causes DNA strand cleavage by free radicals and
inhibits DNA repair by marked inhibition of DNA ligase.
G2-phase specific; also active in late G1, S, and M phases
Metab: tissue-bound, extensive degradation by hydrolysis in
nearly all tissues. Drug & metab products excreted in urine.
Toxicity Dose-limiting: Mild -severe shaking chills & febrile rxns, Bleomycin pneumonitis w/ dyspnea, dry cough
• Common Sensitizes tumor & tissues to radiation, anorexia hyperpigmentation of skin stretch areas, mucositisa.
Dose: 15-unit (mg) vials
Modification. COPD, erythroderma
Doxorubicin (Adriamycin/Rubex/hydroxydaunorubicin)
I: Effective in a large variety of tumors
MOA: Anthracycline; Intercalates b/w DNA base pairs, forms
free radicals, alters cell membranes, induces topoisomerase
II–dependent DNA damage, inhibits preribosomal DNA and
RNA. Cycle–phase nonspecific.
Metab: 70% bound to plasma proteins; metabolized by liver excreted in the bile
Toxicity Dose-limiting: Myelosuppression, Cardiomyopathy
• Common: Alopecia, N/V; stomatitis, ulceration & necrosis.
Dose: 10, 20, 50, 100 & 150mg vials/ 50-75 mg/m2 IV bolus
Modification. congestive heart failure,
Hormones & Hormone Antagonists• diverse group of drugs beneficial in cancer therapy.
• Some alter cellular environment & affect permeability of
cell membrane that will affect cell growth.
• inhibit tumor proliferation by blocking/ antagonizing
naturally occurring substance that stimulates tumor growth.Androgens: testosterone proprionate, methyltestosterone,
fluoxymesterone
Antiandrogens: flutamide
Antiestrogens: tamoxifen
Aromatase inhibitors: aminoglutethimide
Estrogens: diethylstilbestrol, estradiol
Glucocorticoids: prednisone, hydrocortisone, dexamethasone
Gonadotropin inhibitors: leuprolide, goserelin
Progestins: megestrol acetate
Hormones & Hormone AntagonistsAndrogens
I: Breast Ca, short-range anabolic, erythropoiesis stimulant
Toxicity & SE vary; Virilization, fluid retention & hepatotoxic, characterized by abnormal LFTs or cholestasis reversible,
Antiandrogens (bicalutamide, flutamide, nilutamide)
I: Prostate Ca in combination with medical therapy
MOA: Nonsteroidal antiandrogens bind to cytosol androgen
receptors & competitively inhibit uptake or binding
Toxicity Common Impotence, gynecomastia, hypogonadism
Antiestrogens (tamoxifen, toremifene)
I: Breast carcinoma
MOA: Nonsteroidal agents that bind to estrogen receptors,
exert antiestrogenic, estrogenic, or both activities • 3
MiscellaneousMiscellaneous
• BIOLOGICAL RESPONSE MODIFIERS– Interferon-alfa, Interleukin-2
• TYROSINE KINASE INHIBITORS– Imatinib (Glivec): CML
• MONOCLONAL ANTIBODIES– Versus GROWTH FACTOR RECEPTORS
• Rituximab (NHL,CLL), Trastuzumab (metastatic breast CA)
– Versus ANGIOGENIC FACTORS• Bevacizumab (coloretal CA, renal cell CA)
Interferon-a (IFN-a)Sources: Lymphocytes, macrophages, and other cells
Properties: Antitumor activity, Antiproliferative activity,
Inhibition of angiogenesis, Reg’n of differentiation,Interaction
w/ growth factors, oncogenes, other cytokine, enhancement
of tumor-associated antigens; NK cell activation, CTL
activation, induction of (MHC) class I, Antiviral activity
I: CML, hairy cell leukemia, myeloproliferative disorders, cutaneous T-cell lymphomas
D: recombinant forms (IFN-a2a (Roferon-A): 3, 6, 18, & 36million U/mL vials/ IFN-a2b (Intron-A): 3, 5, 18, & 50million U/mL vials
Rituximab (Rituxan)I: Relapsed or refractory low-grade or follicular CD20-(+), B-
cell non-Hodgkin lymphoma
MOA: antibody is a genetically engineered chimeric murine/ human monoclonal antibody directed against CD20 antigen found on the surface of normal and malignant B lymphocytes. In vitro, Fab domain of rituximab binds to CD20 antigen on B lymphocytes, and Fc domain recruits immune effector functions to mediate B-cell lysis.
Metab: detectable in serum 3 to 6 months; admin results in a rapid and sustained depletion of circulating and tissue-based B cells. B-cell levels return to normal by 12 months after completion of treatment.
Toxicity: Dose-limiting. Hypersensitivity rxns, arrhythmias
Common: infusion-related symptom complex responds to slowing infusion rate and consists of fever or chills (50%);
HODGKIN LYMPHOMAHODGKIN LYMPHOMA
ABVD: Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine
BEACOPP: Bleomycin, etoposide, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), procarbazine, prednisone
MOPP: Mechlorethamine, Oncovin (vincristine), procarbazine, prednisone
ChlVPP/EVA Chlorambucil,vincristine (Oncovin), procarbazine, prednisone, etoposide, vinblastine, Adriamycin (doxorubicin)
BREAST CABREAST CA
• AC: Adriamycin (doxorubicin), cyclophosphamide• CA: Cyclophosphamide, Adriamycin (doxorubicin)
(same as AC)• CAF: Cyclophosphamide, Adriamycin (doxorubicin
), fluorouracil (5-FU)• CMF: Cyclophosphamide, methotrexate,
fluorouracil (5-FU)• EC: Epirubicin, cyclophosphamide• FEC: Fluorouracil (5-FU), epirubicin,
cyclophosphamide
COLORECTAL CACOLORECTAL CA
• FOLFOX: Fluorouracil (5-FU), leucovorin (folinic acid), oxaliplatin
• FOLFIRI: Fluorouracil (5-FU), leucovorin (folinic acid), irinotecan
• FL: Fluorouracil (5-FU), leucovorin (folinic acid)