Radiation therapy NSCLC

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. 

Optimal management of locally advanced NSCLC (stages IIB, IIIA, and IIIB) is controversial. Cisplatin-based doublet combinations are recommended for adjuvant and neoadjuvant (preoperative) chemotherapy, with or without concurrent radiation therapy. 

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. 

Aamdal S, Lauvvang G, Owre K, et al. A phase Eli study of docetaxel (Taxotere) combined with concurrent radiation therapy in locally advanced non-small cell lung cancer (NSCLC). Lung Cancer 2000 29(Suppl 1) 100 (abstract 327). 

KomakiR, Seiferheld W, Curran W, etal. Sequential vs. concurrent chemotherapy and radiation therapy for inoperable non-small cell lung cancer (NSCLC) Analysis of failures in a Phase III study (RTOG 94-10) Proc Am Soc Thera Rad Oncol (ASTRO). IJROBP 2000 48 5A (abstr). 

Langer C, Scott C, Byhardt R, et al. Effect of advanced age on outcome in Radiation Therapy Oncology Group studies of locally advanced NSCLC. Lung Cancer 2000 29(Suppl 1)104 A-340. 

Komaki R, Scott CB, Byhardt RW, et al. Failure patterns by prognostic group determined by recursive partitioning analysis (RPA) of 1,547 patients on four Radiation Therapy Oncology Group studies in inoperable non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 1998 42 263-267. 

Adenoviral p53 Gene Transfer with Radiation Therapy in NSCLC... 

The locoregional delivery and efficacy limit the potential therapeutic benefit of Ad-p53 in metastatic Stage IV NSCLC patients except perhaps in a palliative role with low-dose radiation therapy. Currently, ECOG is evaluating the feasibility of Ad-p53 (INGN 201) in combination with 30 Gy of radiation therapy for recurrent or previously radiated NSCLC. This trial initiated by Choy is the first Ad-p53 study to be performed in a cooperative group setting. 

Swisher S, Roth JA, Komaki R, et al. A phase II trial of adenoviral mediated p53 gene transfer (RPR/ INGN 201) in conjunction with radiation therapy in patients with localized non-small cell lung cancer (NSCLC). Am Soc Clin Oncol 2000 19 461a (abstract). 

Uses Pancreatic CA, brain mets, NSCLC, gastric CA Action Antimetabolite -1-ribonucleotide reductase produces false nucleotide base-inhibiting DNA synth Dose 1000 mg/m over 30 min-1 h IV inf/wk x 3-4 wk or 6-8 wk modify dose based on hematologic Fxn (per protocol) Caution [D, /-] Contra PRG Disp Inj SE X BM, N/V/D, drug fever, skin rash Interactions t BM depression W/ radiation therapy, antineoplastic drugs -1- live virus vaccines EMS Monitor for S/Sxs of Infxn OD May cause N/V, p iphOTal tingling, fever and chills symptomatic and supportive... 

Surgery, radiation therapy, and systemic therapy using nonspecific cytotoxic chemotherapy or targeted therapies are all used in the management of NSCLC. Currently, only surgery, and to a lesser extent radiation therapy, offer an opportunity for long-... 

Radiation therapy (radiotherapy) is used in a variety of settings for the treatment of NSCLC. Thoracic radiotherapy may be administered with curative intent for treatment of smaU localized tumors in some patients. Radiotherapy is most commonly administered postsur-gically (adjuvant therapy) for prevention of local disease recurrence, as well as in advanced disease for the palliation of tumor-related symptoms (i.e., control of pain from bone metastases, hemoptysis, or obstructive symptoms). 

Non small cell lung cancer (NSCLC) remains the leading cause of cancer deaths in both men and women in the Western World. NSCLC accounts for approximately 75% of all lung carcinomas and 35% of patients with NSCLC will present with stage lllA or lllB disease. The majority of these patients with mediastinal involvement are not amenable to surgical resection, and primary radiation therapy alone results in 5-year actuarial survival of only 3%-7% and a median survival time of 6-11 months (Jeremic et al. 1996). Combined modality therapy is now considered the standard of care for those patients with unresectable tumors and a good performance status. 

Socinski et al. have reported on their phase I/II experience with dose-escalated thoracic radiation in the setting of a combined modality approach to locally advanced NSCLC (55,64). Two cycles of carboplatin and paclitaxel (AUC 6 and 225 mg/m2/3h q21d) were followed on d 43 by weekly carboplatin and paclitaxel (AUC 2 and 45 mg/ m2/3h x 6) and thoracic radiotherapy (TRT), 50 Gy was delivered to the prechemotherapy tumor volume and areas of suspected microscopic spread in the mediastinum with a 1.0-2.0 cm margin. Boost volumes included the primary tumor volume and all radiographically positive nodes with a 1.0 cm margin. The total dose of radiation was escalated through four cohorts of patients 60,66,70,74 Gy without reaching any of the planned toxicity endpoints. The overall response to the therapy was 50% (3% CR, 47%... 

Modest advances have been seen with the application of chemotherapy to stage 3 (lymph node positive) NSCLC. A few patients with unresectable stage 3A disease can be rendered resectable by chemoradiation using concurrent radiation and cisplatin based therapy. Those who remain unresectable and those with stage 3B disease achieve an approximate 3 month prolongation of overall survival and... 

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