Page 963 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 54 Cancer Chemotherapy 949

ACRONYMS Another class of genes, known as tumor suppressor genes,
may be deleted or mutated, which gives rise to the neoplastic
ABVD Doxorubicin (Adriamycin, hydroxydaunorubicin), phenotype. The p53 gene is the best-established tumor suppressor
bleomycin, vinblastine, dacarbazine
gene identified to date, and the normal wild-type gene appears to
BCNU Carmustine
play an important role in suppressing malignant transformation.
CCNU Lomustine Of note, p53 is mutated in up to 50% of all human solid tumors,
CHOP Cyclophosphamide, doxorubicin (Adriamycin, hydroxy- including liver, breast, colon, lung, cervix, bladder, prostate, and
daunorubicin), vincristine (Oncovin), prednisone skin.
CMF Cyclophosphamide, methotrexate, fluorouracil
COP Cyclophosphamide, vincristine (Oncovin), prednisone
CRC Colorectal cancer CANCER TREATMENT MODALITIES
FAC 5-Fluorouracil, doxorubicin (Adriamycin, hydroxydau-
norubicin), cyclophosphamide With present methods of treatment, when the tumor remains
localized at the time of diagnosis, about one-third of patients
FEC 5-Fluorouracil, epirubicin, cyclophosphamide
are cured with local treatment strategies, such as surgery or
5-FU 5-Fluorouracil
radiotherapy. Earlier diagnosis might lead to increased cure rates
FOLFIRI 5-Fluorouracil, leucovorin, irinotecan with such local treatment. In the remaining cases, however,
FOLFOX 5-Fluorouracil, leucovorin, oxaliplatin early micrometastasis is a characteristic feature, indicating that
MP Melphalan, prednisone a systemic approach with chemotherapy is required for effective
6-MP 6-Mercaptopurine cancer management. In patients with locally advanced disease,
chemotherapy is often combined with radiotherapy to allow for
MOPP Mechlorethamine, vincristine (Oncovin), procarbazine,
prednisone subsequent surgical resection to take place, and such a combined
modality approach has led to improved clinical outcomes. At pres-
MTX Methotrexate
ent, about 50% of patients who are initially diagnosed with cancer
NSCLC Non-small cell lung cancer
can be cured. In contrast, chemotherapy alone is able to cure less
PCV Procarbazine, lomustine, vincristine than 10% of all cancer patients when the tumor is diagnosed at
PEB Cisplatin (platinum), etoposide, bleomycin an advanced stage.
6-TG 6-Thioguanine Chemotherapy is presently used in three main clinical settings:
VAD Vincristine, doxorubicin (Adriamycin, hydroxydaunoru- (1) primary induction treatment for advanced disease or for cancers
bicin), dexamethasone for which there are no other effective treatment approaches, (2)
XELOX Capecitabine, oxaliplatin neoadjuvant treatment for patients who present with localized dis-
ease, for whom local forms of therapy such as surgery or radiation,
or both, are inadequate by themselves, (3) adjuvant treatment to
local methods of treatment, including surgery, radiation therapy,
Several viruses have been implicated in the etiology of various or both.
human cancers. For example, hepatitis B (HBV) and hepatitis C Primary chemotherapy refers to chemotherapy administered
(HCV) are associated with the development of hepatocellular as the primary treatment in patients who present with advanced
cancer; HIV is associated with Hodgkin’s and non-Hodgkin’s lym- cancer for which no alternative treatment exists. This has been the
phomas; human papillomavirus (HPV) is associated with cervical main approach in treating patients with advanced metastatic dis-
cancer, anal and penile cancers, and oropharyngeal head and neck ease, and in most cases, the goals of therapy are to relieve tumor-
cancer; Epstein-Barr virus (EBV), also known as human herpesvi- related symptoms, improve overall quality of life, and prolong
rus 4 (HHV-4), is associated with nasopharyngeal cancer, Burkitt’s time to tumor progression. Studies in a wide range of solid tumors
lymphoma, and Hodgkin’s lymphoma; and Merkel cell polyoma- have shown that chemotherapy in patients with advanced disease
virus (MCV) causes Merkel cell cancer, a rare but aggressive form confers survival benefit when compared with supportive care, pro-
of skin cancer. Expression of virus-induced neoplasia may also viding sound rationale for the early initiation of drug treatment.
depend on additional host and environmental factors that modu- However, cancer chemotherapy can be curative in only a small
late the transformation process. Cellular genes are known that are subset of patients who present with advanced disease. In adults,
homologous to the transforming genes of the retroviruses, a fam- these curable cancers include Hodgkin’s and non-Hodgkin’s lym-
ily of RNA viruses, and induce oncogenic transformation. These phoma, acute myelogenous leukemia, germ cell cancer, and cho-
mammalian cellular genes, known as oncogenes, have been shown riocarcinoma, while the curable childhood cancers include acute
to code for specific growth factors and their corresponding recep- lymphoblastic leukemia, Burkitt’s lymphoma, Wilms’ tumor, and
tors. These genes may be amplified (increased number of gene embryonal rhabdomyosarcoma.
copies) or mutated, both of which can lead to constitutive over- Neoadjuvant chemotherapy refers to the use of chemotherapy
expression in malignant cells. The bcl-2 family of genes represents in patients who present with localized cancer for which alternative
a series of pro-survival genes that promotes survival by directly local therapies, such as surgery, exist but which have been shown to
inhibiting apoptosis, a key pathway of programmed cell death. be less than completely effective. At present, neoadjuvant therapy