Metastatic cancer treatment

The first step in treatment of NSCLC involves confirmation of the clinical stage and determination of resectability of the tumor. This decision always should be made by a thoracic surgeon who routinely performs lung cancer surgery. Treatment options depend on the advancement of disease (i.e., local, locally advanced, or metastatic). 

Chemotherapy is the primary treatment modality for metastatic colorectal cancer (MCRC). Treatment options are generally similar for metastatic cancer of the colon and rectum. 

Oxaliplatin is a third generation diaminocyclohexane platinum analog. Its mechanism of action is identical to that of cisplatin and carboplatin. However, it is not cross-resistant to cancer cells that are resistant to cisplatin or carboplatin on the basis of mismatch repair defects. This agent was recently approved for use as second-line therapy in metastatic colorectal cancer following treatment with the combination of fluorouracil-leucovorin and irinotecan, and it is now widely used as first-line therapy of this disease as well. Neurotoxicity is dose-limiting and characterized by a peripheral sensory neuropathy, often triggered or worsened upon exposure to cold. While this neurotoxicity is cumulative, it tends to be reversible—in contrast to cisplatin-induced neurotoxicity. 

Tan AR et al (2004) Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. J Clin Oncol 22 3080-3090... 

Every Monday in your oncology outpatient department, you run a pharmacist/ nurse-led oral capecitabine clinic, where patients are referred to you by oncologists for pretreatment counselling, drug history-taking and supplementary chemotherapy prescribing (under set clinical management plans) for the adjuvant treatment of colon cancer or treatment of metastatic colorectal cancer. 

Paclitaxel (Taxol ) and its semisynthetic analogue docetaxel (see Figure 5.1) are two of the most important chemotherapeutic drugs, currently used for the treatment of advanced ovarian cancer, metastatic breast cancer, melanoma, non-small-cell lung cancer, and Kar-posi s sarcoma [8,9], More recently, these drugs have been used for the treatment of neck, prostate, and cervical cancers [8, 9],... 

Recent advances in the treatment for cancer of the colon and rectum now offer the potential to improve patient survival but for many patients, improved disease- and progression-free survival represent equally important therapeutic outcomes. Table 127-15 depicts the NCCN Practice Guidelines for chemotherapy for advanced or metastatic colorectal cancer. Although treatment approaches for metastatic colorectal cancer have been historically assessed by their ability to produce a measurable objective tumor response, which is generally believed necessary for any treatment to improve survival, the effects of therapies on survival are clinically more meaningful than their ability to induce a tumor response. However, with the availability of multiple active treatments for metastatic disease, and the likelihood that patients will receive more than one during the course of their treatment, improvements in OS with new therapies wiU be increasingly difficult to determine. 

A 51-year-old woman with metastatic breast cancer started treatment with capeeitabine 2500 mg/m daily for 14 days every 21 days. Treatment was stopped after 8 days because she developed diarrhoea, vomiting and hand-foot syndrome. She improved with parenteral hydration and symptomatic treatment, but 3 weeks later still had diarrhoea, leg oedema and hand-foot syndrome. She was found to have been taking folic acid 15 mg daily for several weeks before starting capecitabine and had continued to take it during and after capecitabine treatment. The patient s condition improved when the folie acid was stopped, but she then developed diarrhoea and fever followed by necrotic colitis and she died from septic shock and vascular collapse. It is possible that the concurrent use of folic acid enhanced the toxicity of capecitabine. ... 

Jakobs et al. [35] reported results on 39 treated patients (17 women, 22 men) that included colorectal cancer, metastatic breast cancer, hepatocellular carcinoma, neuroendocrine tumors, and a mixed group composed of metastatic pancreatic cancer, carcinoma of unknown primary, cholangiocellular carcinoma, thymus carcinoma, malignant melanoma, and choroid melanoma. In this mixed tumor group, two patients were lost for follow-up immediately after treatment. Two patients died before first follow-up 3 months after SIRT (one patient with choroid melanoma and one with carcinoma of unknown primary). However, at the first followup 3-4 months after SIRT, five of six patients presented with stable disease or partial response. The same applied for two of three patients at the followup at 5-6 months. Stable disease was noted in two of three patients at 10-11 months after SIRT. The median time to progression was 8 months (range 3-11 months), although two patients were lost and two died before first follow-up and were therefore not included in this analysis. The median survival was 2.2 months. 

Another area worthy of future investigation is the treatment of non-colorectal, non-neuroendocrine cancers metastatic to the liver. Often referred to as mixed neoplasia, these refer to patients with liver-dominant metastatic disease to the liver from various primaries (breast, melanoma, pancreas, and lung). Although several reports have been described, controlled phase II studies using time-to-progression, tumor response, or progression-free-survival would be clinically relevant given the dearth of options for some of these patients [51-54]. 

Paclitaxel (Taxof ) is a complex plant product derived from the bark of the yew tree, Taxus brevifolia. It is currently indicated for first-line treatment of advanced and metastatic ovarian cancer, metastatic breast cancer (in which it can be given in combination with trastuzumab in patients who... 

Nevertheless, proteinase inhibitors may therefore be useful as therapeutic agents in anti-invasive and anti-metastatic treatment. Studies have shown that potato cysteine proteinase inhibitor PCPI 8.7 inhibited invasion B16 mouse melanoma cell by 21% and serine proteinase inhibitor reduced invasiveness by up to 24 % (Sever et al., 2005). Overexpression of cathepsin B excessively associated with adenocarcinoma of the esophagus and other cancers (Kos Lah, 1998). 

In the veterinary as in the human patient, neoplasms are often metastatic and widely disseminated throughout the body. Surgery and irradiation are limited in use to weU-defined neoplastic areas and, therefore, chemotherapy is becoming more prevalent in the management of the veterinary cancer victim (see Chemotherapeutics, anticancer). Because of the expense and time involved, such management must be restricted to individual animals for which a favorable risk—benefit evaluation can be made and treatment seems appropriate to the practitioner and the owner. In general, treatment must be viewed not as curative, but as palliative. 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

ADCC. Cetuximab is approved for treatment of metastatic colorectal cancer (CRC) and squamous cell carcinoma of the head and neck (SCCHN). Interestingly, an adverse event, acneiform rash seems to correlate with a better response to cetuximab, while there is no such correlation with expression levels of EGFR assessed by immunohistochemistry. Further side effects are rare infusion reactions and hypomagnesia. Two other anti-EGFR antibodies approved for clinical use are the fully human antibody panitumumab (Vectibix)... 

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