Chemotherapy with radiation therapy

Synergistic Cytotoxic Activity of Chemotherapy with Radiation Therapy Concomitant Chemoradiotherapy Multiagent Concomitant Treatment... 

SYNERGISTIC CYTOTOXIC ACTIVITY OF CHEMOTHERAPY WITH RADIATION THERAPY... 

Combining anti-VEGF treatment with chemotherapy or radiation therapy results in a greater anti-tumor effect than either of these therapies alone. 

In addition to their inherent self-sustaining properties, brain tumor stem cells may be more resistant to chemotherapy and radiation therapy than other tumor cells. Bao et al. (2006) found glioma stem cells (CD133+) were relatively radioresistant compared to CD133- tumor cells and preferentially activated the DNA damage checkpoint response. This relative resistance to standard treatment approaches of tumor stem cells compared to the majority of other cells within a tumor may underlie our current inability to cure patients with aggressive brain tumors such as glioblastoma. 

Adjuvant therapy consisting of 5-fluorouracil-based chemotherapy in combination with radiation therapy should be offered to patients with stage II or III cancer of the rectum. 

Long-term follow-up monitors patients for continued disease remission or relapse with careful physical examination of the lymph nodes and sites of prior disease involvement and imaging studies. Patients will have routine chest x-rays and CT scans administered to screen for recurrence of disease. Patients require long-term monitoring for toxicities of their primary treatment, either chemotherapy or radiation therapy. 

A number of studies have evaluated treatment regimens including concurrent chemotherapy and radiation therapy in patients with advanced local stage III nonsmall-cell lung... 

Prior clinical trials have attempted to discern the best manner in which to administer chemotherapy when combined with radiation. It may be given concurrently with standard radiotherapy, an alternating or split-course radiotherapy schedule, or in a sequential fashion as induction (prior to definitive treatment) or adjuvant (following definitive treatment) chemotherapy. Concomitant chemoradiotherapy is the use of both modalities simultaneously. Alternating chemoradiotherapy is the use of systemic chemotherapy for a definitive duration, followed by radiotherapy for a specified period followed by repeated alternations of the two modalities. Split-course chemoradio-therapy usually involves concomitant systemic doses of chemotherapy combined with radiation therapy for a specified duration followed by a rest period, and then the regimen is repeated. This approach allows planned treatment breaks for toxicity recovery. 

A short cell cycle and a high cell proliferation fraction cause the rapid tumor growth and early metastasis. These factors account, in part, for the high sensitivity of SCLC to chemotherapy and radiation therapy. The mean doubling time of SCLC cell lines is 50 d (15-250 d) (15-17). The response to chemotherapy alone is approx 80% but with alow complete response rate of 30 -0% (18). The complete response rate to combination chemotherapy and radiation therapy is up to 80% (19). 

Meta-analyses performed by Pignon et al. and Warde et al. evaluated the improvement of survival and local control with combined chemotherapy and radiation in LD-SCLC (24,25). Local regional failure still remained a principal cause of failure in LD-SCLC occurring in 25-30% although combined local and/or distant recurrence was greater than 50%. Combined chemotherapy and radiation therapy improved survival by 5% and... 

The optimal timing and sequence of combining chemotherapy and radiation therapy is unknown for the treatment of limited-stage small-cell lung cancer. Radiation can be combined with chemotherapy sequentially, alternating, or concurrently. When combined concurrently, radiation can be started early in the treatment or later during the treatment schedule. 

Sequential combinations complete chemotherapy first and then follow it with radiation therapy. The advantages of this schedule are decreased toxicity and increased ability to deliver full doses of chemotherapy. The disadvantage is that there is an increased chance of developing therapy-resistant tumors (36). 

A Japanese trial compared sequential delivery of chemotherapy and radiation therapy to concurrent delivery of chemotherapy and radiation (47). Patients were randomized to receive concurrent hyperfractionated radiation therapy (d 2 of cycle 1 of chemotherapy) or to sequential chemotherapy followed after the fourth cycle by hyperfractionated radiation therapy. The radiation dose was45 Gygivenin 1.5 Gy fractions twice daily for a total of 30 fractions in 3 wk. The chemotherapy given was cisplatin and etoposide. The median survival for the concurrent schedule was 29 mo and for the sequential schedule was 19 mo. The 2-yr survival was 50% for the concurrent therapy and 40% for the sequential therapy (47). These results favored concurrent therapy and are the best results to date for patients with LD-SCLC. 

Current data support the use of concurrent over sequential or alternating chemotherapy and radiation therapy. The optimal delivery of concurrent chemoradiation is still under study. Early delivery of radiation therapy may decrease dissemination by killing the chemoresistant tumor cells prior to their distant seeding. Late delivery of radiation therapy possibly reduces toxicities and full chemotherapy doses can be delivered. However, even with increased toxicity, improved survival rates help establish as standard early delivery of concurrent radiation with platinum-based chemotherapy. 

Chemotherapy and radiation therapy play an important role in the management of colorectal carcinoma. Significant improvements in tumor control and overall survival have been demonstrated with the use of combined-modality therapy in several randomized clinical trials performed over the past 25 yr. This chapter reviews the role of adjuvant chemotherapy and radiation therapy for colon and rectal cancer. Issues surrounding chemoradiation for rectal cancer, including sphincter preservation, total mesorectal excision, local excision, and newer chemotherapy agents, are also discussed. 

The improvement in local control with adjuvant radiation therapy demonstrated in randomized trials does not reach the magnitude seen in retrospective studies. In the postoperative setting, trials have shown a moderate but statistically significant reduction in local failure when comparing radiation to no-radiation arms, but no impact on overall survival (Table 3). In the absence of chemotherapy, pelvic irradiation reduced local failure from 25% to 16% in the first NSABP R-01 trial (24). In the NSABP R-02 study, all patients received some form of 5-FU-based chemotherapy (MOF was available for males), and patients were randomized to pelvic radiation or no radiation. Approximately 75% of patients had transmural primary lesions, although an exact T-stage breakdown was not provided. Local failure was reduced from only 13% to 8% with radiation therapy... 

Russell KJ, Boileau MA, Ireton RC, et al. Transitional cell carcinoma of the urinary bladder histologic clearance with combined 5-FU chemotherapy and radiation therapy. Radiology 1988 167 845-848. 

Studies of Cisplatin-Containing Chemotherapy in Combination with Radiation Therapy Studies of Fluorouracil in Combination with Radiation Therapy... 

Unfortunately, none of the seven randomized trials that have compared radiation therapy alone vs neoadjuvant cisplatin-containing chemotherapy plus radiation therapy demonstrated an improvement in overall or disease-free survival with combined-modality therapy (Table 2). Two studies actually demonstrated poorer survival with neoadjuvant chemotherapy. Souhami et al. (15) reported a significantly poorer survival rate with neoadjuvant chemotherapy in a small trial of patients with stage IIIB disease. This outcome was partly due to increased toxicity and poor compliance in patients who received chemotherapy. Another trial of neoadjuvant epirubicin and cisplatin was closed early when interim analysis revealed a significantly higher recurrence rate in the chemotherapy arm (16). These trials fail to provide any evidence that sequential cisplatin-containing chemotherapy and radiation therapy are of benefit. Possible explanations for the disappointing results include the effects of chemotoxicity, altered compliance, and possible accelerated repopulation of resistant clones after neoadjuvant chemotherapy. 

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