Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum

Abstract

The Gastrointestinal Tumor Study Group's (GITSG) adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5-fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease-free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P less than 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single-modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

Analysis of Early Postoperative Morbidity Among Patients with Rectal Cancer Treated with and without Neoadjuvant Chemoradiotherapy

“…In our own experience, and in agreement with other published studies, 14,15,[31][32][33] we consider that preoperative chemoradiotherapy does not increase either the number of early postoperative complications or the rate of surgical mortality. We should be cautious with these results because ours is not a randomized, double-blind study.…”

“…Although this fact could be related to the synergistic effect of the two modalities, the correlation between neoadjuvant toxicity and postoperative complications has not been clearly determined. 31,32 We have found a dose-and time-dependent correlation, although it is not statistically significant, between radiation and some postoperative complications. When analyzed individually, those patients in group A with general complications, wound infection, intraabdominal abscesses, and anastomotic leak had received a higher mean dose of radiotherapy and had experienced a longer time interval between neoadjuvant therapy and surgery.…”

Preoperative Combined Radiotherapy and Chemotherapy for Middle and Lower Rectal Cancer: Preliminary Results

“…5 However, this treatment method has been questioned because, in 61% of patients, it causes toxicity that is severe, life threatening, or fatal. 6 Moreover, almost 35% of the patients in the above trials did not complete all the chemotherapy cycles planned. 2,3 Short-course preoperative radiation treatment alone (25 Gy in 1 week) is accompanied by a lower local recurrence rate 7,8 ; moreover, according to the recent Swedish Rectal Cancer Trial, 9 it is also followed by a better OS; after a minimum follow-up time of 5 years, 58% of patients who had received preoperative RT were alive, compared with 48% in the surgery-alone control group.…”

Influence of Treatment Technique on Dose-Volume Histogram and Normal Tissue Complication Probability for Small Bowel and Bladder A Prospective Study Using a 3-D Planning System and a Radiobiological Model in Patients Receiving Postoperative Pelvic Irradiation

“…Many factors have suggested to be potentially associated with the tolerance of small bowel to external radiation. These include hypertension [18], diabetes mellitus [16], pelvic inflammatory disease [30], body habitus [19], prior abdominal or pelvic surgery [13], simultaneous chemotherapy [28]. Various surgical means were developed to reduce the irradiated risk organ volume.…”