Lung cancer small-cell, treatment

The two taxanes currently in use are paclitaxel, which is used in the treatment of ovarian cancer and metastatic breast cancer and docetaxel, which is used to treat metastatic breast cancer, small cell lung cancer and prostate cancer. 

The efficacy of iproplatin for the treatment of ovarian cancer, small cell lung carcinomas, and advanced squamous cervical carcinomas has been evaluated in the United States and in Great Britain. 

Podophyllotoxin 87, isolated from Podophyllum species shows antitumor properties it inhibits microtubule assembly, in vivo, the result of which is the destruction of the cytoskeleton in the cytoplasm. As a consequence, the cell division is stopped at the mitotic stage of the cell cycle (3), Semi-synthetic derivatives of podophyllotoxin, i.e., Etoposide 88 and Teniposide 89 have been developed. Tliey do not possess the toxicity of podophyllotoxin 87 and are now being used (alone or in conjunction with odier drugs) in treatment for germinal testicular cancer, small cell lung cancer, and certain form of leukemia (3), They have been shown to induce, both, in... 

The majority of promising drug candidates emerging from marine natural products research to date are potential cancer treatments. Six anti-cancer compounds that are either marine natural products or synthetic analogs of marine natural products have made it to clinical trials. The first of these compounds to enter clinical trials was didemnin B (43), one of a family of cyclic depsipetides isolated from the Caribbean tunicate Trididemnum solidum Didemnin B was advanced to Phase II clinical trials for treatment of small cell lung cancer, myeloma, prostate cancer, and melanoma. Unfortunately, no favorable responses were found so the compound has been withdrawn. Crude extracts of another Caribbean tunicate, Ecteinascidia turbinata, showed extremely... 

The usual dose consists of 1000 mg/m2 i.v. It is the most active single agent for treating pancreatic cancer, and it is used as a fust-line treatment for both pancreatic and small cell lung cancers. The dose-limiting toxicity is bone marrow suppression. 

The vesicant vinorelbine is structurally similar to vincristine and may cause many of the same side effects as vincristine. While this vesicant is administered intravenously over 6 to 10 minutes, patients should be counseled about neuropathy, ileus, and myelosuppression. The pharmacokinetics of vinorelbine are best described by a three-compartment model, with an a half-life of 2 to 6 minutes, a 3 half-life of 1.9 hours, and a y half-life of 40 hours. Vinorelbine has shown efficacy in the treatment of breast cancer and non-small cell lung cancer. Additional side effects include myelosuppression, paresthesias, and mild nausea and vomiting. 

Docetaxel, another taxane, binds to tubulin to promote microtubule assembly. The pharmacokinetics of docetaxel are best described by a three-compartment model, with an a half-life of 0.08 hours, a 3 half-life of 1.6 to 1.8 hours, and a terminal half-life of 65 to 73 hours.14 Docetaxel has activity in the treatment of breast, non-small cell lung, prostate, bladder, esophageal, stomach, ovary, and head and neck cancers. Dexamethasone, 8 mg twice daily for 3 days starting the day before treatment, is used to prevent the fluid retention syndrome associated with docetaxel and possible hypersensitivity reactions. The fluid... 

Vinorelbine, a microtubule interactive agent, also has shown impressive response rates in metastatic breast cancer.60 Vinorelbine was approved by the FDA in 1994 for the treatment of non-small cell lung cancer. It is not approved for breast cancer, but response rates to vinorelbine range from 30% to 50%, with an overall 5% complete response rate in phase I and phase II studies in patients with advanced breast cancer. Importantly, paclitaxel, docetaxel, and vinorelbine do not appear to be cross-resistant with anthracyclines, which are arguably considered first-line treatment of metastatic breast cancer. 

Surgical resection of the tumor is the mainstay of treatment in early-stage non-small cell lung cancer and produces the longest survival rates. 

There are four major histologic types of lung cancer that are divided into two classes based on response to treatment and prognosis small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). However, it is important to note that certain other rare malignancies can be seen as well as mixed-type carcinomas. The four major types of lung cancer are outlined in Table 87-1. 

FIGURE 87-1. Clinical pathway for non-small cell lung cancer. See text for specific treatment recommendations. 

Small cell lung cancer typically presents as extensive disease (approximately 60% to 70% of new cases) and progresses very quickly. Small cell carcinomas are very responsive to chemotherapy and radiation. Radiotherapy became the standard in 1969, when a randomized trial showed that it offered the potential for cure, whereas surgery did not.20 For the vast majority of patients, chemotherapy with or without radiotherapy is the treatment of choice. Even after a complete response to therapy, the cancer usually recurs within 6 to 8 months, and survival time following recurrence is typically short ( 4 months). This yields a typical survival rate of 14 to 20 months for limited disease and 8 to 13 months for extensive disease.33 Table 87-6 illustrates the general treatment path of SCLC. 

TABLE 87-6. Small Cell Lung Cancer Treatment Overview60... 

Radiation therapy is the treatment of choice for chemotherapy-resistant tumors such as non-small cell lung cancer (NSCLC) or in chemotherapy-refractory patients with SVCS. Between 70% and 90% of patients will experience relief of symptoms. Radiation therapy also may be combined with chemotherapy for chemotherapy-sensitive tumors such as SCLC and lymphoma. In the rare emergency situations of airway obstruction or elevated intracranial pressure, empirical radiotherapy prior to tissue diagnosis should be used. In most patients, symptoms resolve within 1 to 3 weeks. 

Currently in phase II clinical trials as a treatment for melanoma, hepatocellular carcinoma, and non-small-cell lung cancer (Hamann 2004), the compound has a mode of action that is not well understood, though it has been deemed necrosislike and characterized by cytoplasmic swelling and DNA clumping (Janmaat et al. 2005). 

In October 2003, the SFDA approved the world s first gene therapy— Gendicine (a recombinant human adenovirus type 5 mediated delivery of p53 gene)— for the treatment of head and neck cancer. In 2005, another head and neck cancer drug, Oncorine (a recombinant oncolytic adenovirus type 5), was approved. In the same year, another recombinant human endostatin, Endostar, was approved for the treatment of small-cell lung cancer. 

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