Chemotherapy

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Contents 1 More Specific Terms 2 Introduction 3 Indications 4 Adverse-effects 5 Mechanism-of-action 6 More General Terms 7 Additional Terms 8 References

More Specific Terms

• chemotherapy for breast cancer
• neoadjuvant chemotherapy

Introduction

• Treatment of disease with chemicals or pharmaceutical agents, generally used in reference to treatment of neoplastic disease.

Indications

• curable by chemotherapy

• acute lymphoblastic leukemia
• acute myeloid leukemia
• Ewing's sarcoma
• gestational trophoblastic carcinoma
• Hodgkin's disease
• non-Hodgkin's lymphoma

• Burkitt's lymphoma
• diffuse large cell lymphoma
• lymphoblastic lymphoma

• rhabdomyosarcoma
• testicular carcinoma
• Wilm's tumor

• chemotherapy is beneficial

• anal carcinoma
• bladder carcinoma
• breast carcinoma
• chronic lymphocytic leukemia
• chronic myelogenous leukemia
• hairy cell leukemia
• head & neck carcinoma
• small cell carcinoma of the lung
• multiple myeloma
• follicular lymphoma
• ovarian carcinoma

• chemotherapy may have some benefit

• astrocytoma
• cervical carcinoma
• colorectal carcinoma
• hepatocellular carcinoma
• Kaposi's sarcoma
• non-small cell carcinoma of the lung
• melanoma
• pancreatic carcinoma
• prostate carcinoma
• soft tissue sarcoma

• ADJUVANT chemotherapy is beneficial

• breast carcinoma
• colorectal carcinoma, stage III
• osteogenic sarcoma
• ovarian carcinoma, stage III
• testicular carcinoma

Adverse-effects

• see specific agent
• generally toxicity to rapidly dividing cells:

• bone marrow
• gastrointestinal mucosa
• hair follicles

• myelosuppression: most cytotoxic drugs
• nausea/vomiting: cisplatin doxorubicin, cyclophosphamide
• diarrhea: 5FU, capecetabine, ironotecan
• alopecia: doxorubicin, cyclophosphamide, paclitaxel
• mucositis, stomatitis: doxorubicin, methotrexate
• vesicant: doxorubicin, mitomycin
• peripheral neuropathy:

• paclitaxel, docetaxel, cisplatin, vincristine

• pulmonary toxicity: bleomycin, mitomycin
• nephrotoxicity: cisplatin, ifosfamide
• cardiotoxicity: doxorubicin
• gonadal toxicity: alkylating agents ( cyclophosphamide)
• carcinogenicity:

• alkylating agents, etoposide, doxorubicin ( AML)
• cyclophosphamide ( bladder cancer)
• tamoxifen ( endometrial cancer)

• extravasation injury: anthracyclines; vinca alkaloids

Mechanism-of-action

• interference with DNA synthesis

• purine/ pyrimidine analogues

• 5-fluorouracil
• 6-thioguanine

• methotrexate

• DNA-binding

• alkylating agents

• cyclophosphamide
• cisplatin
• chlorambucil
• melphalan

• intercalating agents

• doxorubicin
• bleomycin
• mitomycin
• etoposide ( VP-16)

• microtubule inhibition

• vinca alkaloids

• vincristine
• vinblastine

• paclitaxel (Taxol)

• recruitment of cytotoxic immune-cells (investigational)

• bifunctional antibodies that link natural killer-cells with cancer cells [4]
  

• * Generally, chemotherapy effective on replicating cells.
  
• Mechanism of chemotherapy failure:

• tumor cell heterogeneity

• cells resistant to chemotherapeutic agents
• decreased drug uptake
• increased drug efflux

• multidrug resistance -> P-glycoprotein

• decreased drug activation
• increased drug inactivation
• increased production of target enzyme

• large number of non-cycling or resting cells
• pharmacologic sanctuaries

• blood-tissue barriers
• blood supply-tumor barriers

More General Terms

• pharmacologic therapy

Additional Terms

• adjuvant
• antineoplastic agent (chemotherapeutic agent)
• chemotherapy consolidation
• combination chemotherapy
• induction
• multidrug-resistance
• vaccination with intense chemotherapy

References

1. Stedman's Medical Dictionary 27th ed, Williams & Wilkins, Baltimore, 1999
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 678-680
3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 527
4. Bargou R et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008 Aug 15; 321:974. PMID: [1]
5. Scholl C et al Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 2009 May 29; 137:821 PMID: [2]
   - Luo J et al A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 2009 May 29; 137:835. PMID: [3]
6. Cancer Chemotherapy: NIH Institute and Center Resources [4]
7. National Guideline Clearinghouse
   - The role of erythropoietin in the management of cancer patients with non-hematologic malignancies receiving chemotherapy ngc-guideline: [5]
   - Chemotherapy and biotherapy: guidelines and recommendations for practice. (Oncology Nursing Society) ngc-guideline: [6]
   - American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants ngc-guideline: [7]

chemotherapy