Nonsmall cell cancers

LRP1B Loss-of-function (sporadic) Esophageal squamous cell carcinoma, nonsmall-cell lung cancer... 

Belagen pu matucel-L Anti-TGF-(32 vaccine TGF- 32 Nonsmall-cell lung cancer... 

Selective bioreductive alkylation in high DT-diaphorase cancer types (melanoma renal and nonsmall-cell lung cancers)15 would exhibit maximal antitumor activity with minimal side effects. 

Takanami, I. Overexpression of CCR7 mRNA in nonsmall cell lung cancer correlation with lymph node metastasis. Int J Cancer 2003 105 186-189. 

Brognard, J., Clark, A.S., Ni, Y., and Dennis. P.A. 2001. Akt/protein kinase b is constitutively active in nonsmall cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. 

Choi, J.H., Kim, C., Lim, H. Y. et al. 2001. Vascular endothelial growth factor in the serum of patients with nonsmall cell lung cancer Correlation with platelet and leukocyte counts. Lung Cancer 33 171-179. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

Preliminary evidence suggest that c-erbB-2 may also be a prognostic marker for other cancers such as gastric (Y2), ovarian (S7), cervical (K5), and nonsmall cell carcinoma of the lung (K3). Thus, c-erbB-2 has the potential to be a prognostic marker for many different types of adenocarcinomas. 

Hirsh V, Desjardins P, Needles BM, Rigas JR, Jahanzeb M, Nguyen L, Zembryki D, Leopold LH (2007) Oral versus intravenous administration of vinorelbine as a single agent for the first-line treatment of metastatic nonsmall cell lung carcinoma (NSCLC) - A randomized phase II trial. American Journal of Clinical Oncology-Cancer Clinical Trials 30 245-251. 

Ciardiello F, De Vita F, Qrditura M, et al. The role of EGFR inhibitors in nonsmall cell lung cancer. Curr Opin Oncol 2004 16 130-5. 

The short chain fatty acids include butyrate derivatives Hke phenylbu-tyrate, AN-9 (pivaloyloxymethyl butyrate) and valproate. Unfortimately, these compounds have poor potency and pharmacokinetic properties, including short half-life. Numerous Phase I studies with phenylbutyrate, in various oral and intravenous schedules [118-120] have been performed, with neurological toxicity at higher doses being reported. AN-9 showed initial promise in a Phase I study, where the MTD was not reached [121]. The subsequent Phase II study in nonsmall cell lung cancer in 47 patients resulted in fatigue, nausea and dysgeusia as common toxicities. Three partial responses (PR)... 

Swisher SG, Roth JA, Nemunaitis J, et al. Adenovirus-mediated p53 gene transfer in advanced nonsmall-cell lung cancer. J Natl Cancer Inst 1999 91(9) 763—771. 

Takeda et al. (64) performed a phase I/II study consisting of low-dose CDDP (6-10 mg/m2/d) and UFT (600 mg/d) combined with radiotherapy (50 Gy/25 fractions) as postoperative adjuvant therapy following curative resection for patients with nonsmallcell lung cancer (NSCLC). The combined therapy was well tolerated and resulted in a disease-free survival rate of 78% at 2 yr. Another study in a small number of patients with unresectable stage III nonsmall-cell lung cancer, UFT (400 mg/m2 on d 1-52) and CDDP (80 mg/m2 on d 8,29, and 50) were administered with radiation therapy (total dose of 60.8 Gy in 38 fractions on d 1-52). Among 17 evaluable patients, 94% (16 patients) achieved partial responses with median time to tumor progression of 30 wk, and the... 

Early clinical studies clearly demonstrated that cisplatin could be administered safely and concurrently with radiation therapy (73-75). Early clinical trials that demonstrated the promise of the combination of cisplatin and radiation therapy included the treatment of brain tumors (76,77), head and neck tumors (78), malignant melanoma (79), and bladder cancer (80). Early clinical trial integrating carboplatin administration with radiation therapy was carried out in patients with locally advanced nonsmall cell lung cancer (NSCLC) (81). A hypothesis put forth by Coughlin and colleagues (81) was that the best clinical outcomes would be achieved with the combination of cisplatin and radiation therapy in tumors that were responsive to cisplatin. 

The earliest combination chemotherapy and radiation trials in nonsmall-cell lung cancer included cisplatin and 5-fluorouracil and concurrent radiation therapy and found survival results comparable to those for sequential chemotherapy and radiation or to daily cisplatin and radiation therapy without surgery (119,121). Phase II studies of stage Ilia and Illb nonsmall-cell lung cancer patients treated with the combination of cisplatin with etoposide and 5 -fluorouracil and either single daily radiation fractionation or twice daily radiation fractionation prior to surgery produced similar clinical results (119,121). Complete surgical resection was accomplished in 70% of the patients, the median survival was 22 mo and the 2-yr survival rate was 45%. 

Radiosensitizing Abilities of the Taxanes Application in the Clinic Nonsmall-Cell Lung Cancer Small-Cell Lung Cancer Brain Tumors Genitourinary Cancers Gynecological Cancers Breast... 

Lau et al. have reported on their experience of administering radiation with taxol dosed twice a week for locally advanced nonsmall-cell lung cancer (53). Their phase II trial was conducted combining low-dose radiosensitizing chemotherapy with concurrent radiation followed by consolidation chemotherapy (62). The induction chemoradiation consisted of paclitaxel, 30 mg/m2 iv over 1 h, twice weekly for 6 wk carboplatin, AUC of... 

There is certainly less data available on the role of concurrent docetaxel with radiation in the treatment of locally advanced nonsmall-cell lung cancer. Koukourakis et al. (66) have reported on their phase I/II experience of administering radiation concurrently with docetaxel for stage IIIB NSCLC. In the phase II portion of their study, 30 mg/m2 of docetaxel was given weekly with concurrent 64 Gy of thoracic radiation. Esophagitis was the main side effect of the regimen wherein 17% of patients needed a two-week treatment delay and another 31 % of patients required minor delays (3-7 d). Thirty-five patients were enrolled and evaluable, and the overall response rate was 80% (34% CR). The median survival was 12 mo, and 1-yr survival rate was reported as being 48%. 

Choy H, Shyr Y, CmelakAJ, MohrPJ, Johnson DH. Patterns of practice survey for nonsmall-cell lung carcinoma in the U.S. Cancer 2000 88(6) 1336-1346. 

Socinski M A, Rosenman JG, Schell MJ, et al. Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall-cell lung carcinoma a modified Phase I trial. Cancer 2000 89(3) 534-542. 

Topotecan has radiation-sensitizing properties demonstrated in log- and plateau-phase cell cultures (23,36) and in murine fibrosarcomas (37,38). Trials have begun in patients with nonsmall-cell lung cancer (NSCLC) and in those with central nervous system (CNS) tumors. 

Graham MV, Jahanzeb M, Dresler CM, Cooper JD, Emami B, Mortimer JE. Results of a trial with topotecan dose escalation and concurrent thoracic radiation therapy for locally advanced, inoperable nonsmall-cell lung cancer. Int J Radiat Oncol Biol Phys 1996 36(5) 1215-1220. 

Scalliet P, Goor C, Galdermans D, et al. Gemzar (Gemcitabine) with thoracic radiotherapy—A phase II pilot study in chemonaive patients with advanced nonsmall-cell lung cancer (NSCLC). Pro Am Soc Clin Oncol 1998 17 abstract 1923. 

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