Radiation acute toxicity

A similar small phase II trial from Germany has reported on seven patients receiving concurrent chemoradiation for transitional cell carcinoma of the bladder with cisplatin and paclitaxel (96). The authors conclude that this combination is at least feasible given an acceptable acute toxicity profile and reasonable efficacy. Another small series is reported by Nichols et al. (97) where eight patients received radiation with concurrent paclitaxel and carboplatin in an attempt at bladder preservation. Three of the patients remain free of distant metastases, and local recurrence has occurred in three. 

The rationale for concurrent chemoradiation is that the ChT can augment local-regional control by both direct tumor cell killing and radiosensitization at the same time as it addresses systemic micrometastases. Unfortunately, this also has the potential to increase radiation-related mucosal acute toxicity, predominantly esophagitis and pneumonitis. Thus, some of the early trials of concurrent therapy used either attenuated dose ChT or split course RT to ameliorate potential cotoxicity. These trials showed that concurrent therapy is feasible and, as with the sequential approach, improves outcome. 

Valentini V, Coco C, Cellini N, et al. Preoperative chemoradiation for extraperitoneal T3 rectal cancer acute toxicity, tumor response, and sphincter preservation. Int J Radiat Oncol Biol Phys 1998 40 1067-1075. 

Many of the effector functions of the immune system are dependent on a multitude of cell types, which all share a common precursor, the pluripotent stem cell. Therefore, any damage to the stem cell would be expected to have devastating consequences, several of which would extend beyond the immune system, most notably involving the red blood cell. Fortunately, the stem cell is refractory to xenobiotic-in-duced perturbation and is only affected by high doses of radiation. However, subsequent steps of hematopoiesis are affected by exposure to chemicals, with benzene being a classic example. Acute toxicity to benzene is associated with pancytopenia, aplastic anemia, and, at high doses, immunosuppression and leukemia. 

Komaki R, Lee JS, Milas L et al. (2004) Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer report of a randomized comparative trial. Int J Radiat Oncol Biol Phys 58 1369-1377... 

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