Chemotherapy locally advanced

Erlotinib (Tarceva ) competes with ATP in the HER1/EGFR ATP-binding pocket. It is used in the clinic in locally advanced or metastatic non-small cell lung cancer after failure of at least one chemotherapy regime [1, 3, 5]. 

Neoadjuvant chemotherapy is appropriate for patients with locally advanced or inflammatory breast cancer, followed by local therapy and further adjuvant systemic therapy. 

The use of preoperative systemic therapy is gaining favor in both early-stage and locally advanced breast cancers. This approach to therapy, referred to as neoadjuvant or primary systemic therapy, most often consists of chemotherapy but in special circumstances also may include hormonal therapy (e.g., in inoperable patients with significant comorbidities). The advantages of preoperative systemic therapy include... 

Locally advanced breast cancer often is treated with neoadjuvant therapy to make the tumor surgically respectable. During neoadjuvant chemotherapy, laboratory values to monitor chemotherapy toxicity are obtained prior to each cycle of chemotherapy, and a physical examination and ultrasound exams to detect size of tumor are performed after the cycles of neoadjuvant therapy are completed. After a complete surgical resection, monitoring proceeds as described earlier for early breast cancer. 

The goal of neoadjuvant chemotherapy in locally advanced breast cancer is cure. Complete pathologic response, determined at the time of surgery, is the desired end point. 

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. 

Kafka, A., Sauer, G., Jaeger, C., et al. (2003) Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer. Int. J. Oncol. 22, 1117-1121. 

Bartehnk H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997 15 2040-2049. 

Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999 340(15) 1144—1153. 

Rivera F, Lopez-BreaM, Lopez-Vega J, PascualC, Rubio A, etal. High activity of UFT vinorelbine and cisplatin (UFTVP) as induction chemotherapy for locally advanced squamous cell head and neck carcinoma (SCHNC). ProcAm Soc Clin Oncol 1997 16 386a (abstr 1376). 

Brizel DM, Alberx MF, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998 338 1798-1804. 

Belani CP, Aisner J. Combined chemotherapy and radiation in locally advanced non-smah ceh lung cancer. Semin Oncol 1994 21(Suppl 12) 79-90. 

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... 

Suntharalingam M, Haas ML, Van Echo DA, et al. Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck. Cancer 2001 91(3) 548-554. 

Posner MR, Glisson B, FrenetteG, etal. Multicenter phase I-II trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy for patients with locally advanced squamous cell cancer of the head and neck. J Clin Oncol 2001 19 1096-1104. 

Eberhardt W, Wilke H, Stamatis G, et al. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small cell lung cancer. Mature results of a phase II trial. J Clin Oncol 1998 16 622-634. 

Pritchard RS, Anthony SP. Chemotherapy plus radiotherapy compared with radiotherapy alone in the treatment of locally advanced, unresectable, non-small cell lung cancer A meta-analysis. Ann Intern Med 1996 125 723-729. 

Komaki R, Scott C, Ettinger D, et al. Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall-cell lung cancer Radiation Therapy Oncology Group (RTOG) 92-04. Int J Radiat Oncol Biol Phys 1997 38 149-155. 

A landmark trial was an intergroup study (RTOG 85-01) in which patients with locally advanced esophageal cancer were randomized to chemotherapy and radiation or radiation alone. Chemotherapy consisted of 5-FU (1000 mg/m2/24 h x 4 d) and cisplatin (75 mg/m2, d 1). Radiation therapy (5000 cGy/25 fractions) was initiated concurrently with d 1 of chemotherapy. Chemotherapy was given q 4 wk during radiation (cycles 1, 2) and q 3 wk following radiation (cycles 3,4). The radiation alone arm consisted of 6400 cGy/32 fractions. Only 50% of patients were able to complete all four cycles of chemotherapy. 

The management of locally advanced breast cancer requires the integration of surgery, chemotherapy, and radiation therapy. This chapter summarizes the existing experience and addresses some of the remaining issues in combined modality therapy of locally advanced and inflammatory breast cancer. 

Merajver SD, Weber BL, Cody R, et al. Breast conservation and prolonged chemotherapy for locally advanced breast cancer the University of Michigan experience. J Clin Oncol 1997 15 2873-2881. 

Honkoop AH, Luykx-de Bakker SA, Hoekman K, et al. Prolonged neoadjuvant chemotherapy with GM-CSF in locally advanced breast cancer. Oncologist 1999 4 106-111. 

Eltahir A, Heys SD, Hutcheon AW, et al. Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy. Am J Surg 1998 175 127-132. 

Schwartz GF, Birchansky CA, Komamicky LT, et al. Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast. Cancer 1994 73 362-369. 

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