Cancer Chemotherapy

·         IMP REGIMES:

o   ABVD: Doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine – Hodgkin’s disease

o   MOPP: Mechlorethamine, vincristine (oncovin), procarbazine, prednisone :Hodgkin’s disease

o   CHOP: Cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (oncovin), prednisone: Non‑Hodgkin's lymphoma or CLL

o   COP: Cyclophosphamide, vincristine (oncovin), prednisone ‑ CLL

o   CMF: Cyclophosphamide, methotrexate, fluorouracil :Breast carcinoma

o   FAC: Fluorouracil, doxorubicin (adriamycin), cyclophosphamide :Breast carcinoma

o   FEC: Fluorouracil, epirubicin, cyclophosphamide :Breast carcinoma

o   IFL: Irinotecan, fluorouracil, leucovorin :Colorectal carcinoma +/‑ oxaliplatin

o   MP: Melphalan, prednisone :Multiple myeloma

o   VAD: Vincristine, doxorubicin (adriamycin), dexamethasone :Multiple myeloma

o   PCV: Procarbazine, lomustine (CCNU), vincristine :brain tumors like oligodendroglioma

o   BEP: Cisplatin (platinum), etoposide, bleomycin :Testicular carcinoma (previously PVB)

o   FOLFIRI: Fluorouracil, leucovorin, irinotecan

o   FOLFOX: Fluorouracil, leucovorin, oxaliplatin

o   VAD: Vincristine, doxorubicin (Adriamycin), dexamethasone

o   XELOX: Capecitabine, oxaliplatin

o    

o   Hodgkin - ABVD, MOPP (Curative)

o   Non-Hodgkin – CHOP-R

o   CLL - CHOP, COP

o   Breast - CMF, FAC, FEC

o   Colorectal - IFL

o   Multiple Myeloma - MP, VAD

o   Brain - PCV

o   Testes – PEB

o   Retinoblastom: CEV  carboplatin, etoposide, and vincristine

o   T-10 protocol of OSA: MO ABCD :Mtx, Oncovin, ActD, Bleomycin, Cisplatin, Doxorubicin

o   Averbuch's chemotherapy protocol for PheoChrmocytoma includes dacarbazine, cyclophosphamide, and vincristine, repeated every 21 days for three to six cycles.

o    

·         BAHEAP (Bah-Heap) = Antimetabolites, Antimitotics, Procarbazine, Bleomycin, Etoposide, Hydroxyurea = CC-specific

·         VECMN (Pronounced Vec-Man, like Pac-Man) = Nitrosoureas, Cytarabine, Methotrexate, Etoposide, Vincristine = CNS

·         Antibiotics = BADIE (Bleomycin, Actinomycin, Doxorubicin, Irinotecan, Etoposide, because antibiotics are used for bacteria and bacteria are bad

·         Chemotherapeutic agents that may cause parkinsonism: The interleukins (alpha-interferon and IL-2) and hexamethylmelamine.

·         Hormonal drug may cause retinopathy: Tamoxifen may result in retinopathy after prolonged use.

·         Chemotherapeutic agents that may induce TTP: Bleomycin, cisplatin, and mitomycin-C have been reported to trigger TTP.

·         Reversible posterior leukoencephalopathy syndrome (RPLS): FK506 (tacrolimus) and cyclosporine.

·         Two drugs that enhance leukoencephalopathic changes induced by radiation therapy:  Methotrexate and cytosine arabinoside may enhance leukoencephalopathy. Both drugs may induce this problem without prior radiation therapy.

·         Mucositis is most commonly associated with 5-FU, methotrexate, and doxorubicin.

·         Chemotherapy-induced thrombocytopenia:

 When platelet counts drop below 20,000/mm3, there is increased risk for intracranial hemorrhage. Platelet transfusions are usually indicated when the platelet count drops to <10,000/mm3, or possibly sooner if the patient experiences signs or symptoms of hemorrhage.

·         Cytokine release syndrome: Muromonab

·         A vesicant is an agent that produces a vesicle; in oncology, it is a chemotherapeutic drug that can cause a severe burn if the drug infiltrates around the intravenous catheter. The anthracyclines (doxorubicin, daunorubicin), dactinomycin, and the vinca alkaloids (vincristine, vinblastine) are all vesicants. These drugs must be administered either through a central venous catheter or through a newly placed, free-flowing intravenous catheter that does not cross over a joint space.

·         Transient symptoms attributed to temporary demyelination have been observed 6-8 weeks following completion of central nervous system (CNS) radiation, most commonly for CNS prophylaxis for acute lymphoblastic leukemia (ALL). Children who develop the "somnolence syndrome" have lethargy, headache, and anorexia that last for about 2 weeks. Computed tomography and cerebrospinal fluid studies show no consistent abnormality, but an electroencephalogram will often reveal a slow-wave activity consistent with diffuse cerebral disturbance. The use of steroids during irradiation appears to minimize the occurrence of the syndrome.

·         Important note: Vincristine differs from the other two vinca alkaloids, vinblastine and vinorelbine, which do cause bone marrow suppression (and not neuropathies) as their main dose-limiting toxicity.

·         One of several problems with imatinib therapy is that it is a substrate and rather powerful inhibitor of several cytochromes (CYP3A4, 2C9, and 2D6), which are important for the metabolism of many other drugs—warfarin, theophylline, and many others— whose actions can be increased excessively if dosages are not adjusted accordingly. Conversely, imatinib is a target of interactions by this mechanism. Phenytoin, carbamazepine, barbiturates, and rifampin are examples of drugs that can induce imatinib metabolism and reduce the clinical response to it; and such drugs as azole antifungals and erythromycin can reduce imatinib’s clearance and increase the risk of toxicity.

·         Gompertzian analysis (a plot of the log of the number of cancer cells in a tumor vs. time) shows that after a tumor has reached a certain size, the rate of tumor growth (and “overall metabolic rate”) slows: lower growth fraction or, stated differently, the longer it takes for the tumor to double in size. This slowed growth is partially due to more cells entering the G0 (resting) phase of the cell cycle, where responsiveness to many chemotherapeutic agents is low. (One reason for this is the sheer size of the tumor as related to blood flow and the delivery of nutrients that the rapidly dividing cells need. Reduced nutrient and oxygen delivery not only reduces cell replication, but also delivery of the chemotherapeutic agents.)

·         Flutamide, by blocking androgen receptors, prevents the potential worsening of the tumor in the early phase of leuprolide therapy when testosterone levels rise.

·         Asparaginase is an enzyme that catalyzes the hydrolysis of serum asparagine to aspartic acid and ammonia. Major toxicities from asparaginase are related to antigenicity (it is a foreign protein, and some fatal anaphylactic reactions have occurred), pancreatitis, and a 50% incidence of some hepatic dysfunction based on the presence of elevated serum transaminases. The drug, which is largely G1 phase-specific, is not cytotoxic to cells other than leukemic lymphoblasts. Host (and other cells) can synthesize and replace asparagine that has been hydrolyzed by the drug; the lymphoblasts cannot, and so they are killed.

·         FYI:

Cisplatin: hearing loss and nephrotoxicity.

Vincristine: hearing loss, but nephrotoxicity is very rare

methotrexate can cause nephrotoxicity, but it does not cause hearing loss

·         Be sure you remember that the metabolic detoxification of azathioprine and 6-mercaptopurine depends in part on xanthine oxidase. Inhibiting that enzyme with allopurinol, therefore, may increase the risk of toxicity to host cells.

·         Mechlorethamine, like cyclophosphamide (and carmustine and several others), is an alkylating agent. They are called bifunctional alkylating agents because they can covalently bind to DNA in two places (“nucleophilic attack”), thereby forming cross-links between two adjacent strands or between two bases in one strand. This ultimately disrupts DNA and RNA synthesis or may cause strand breakage.