NorwayPreoperative Chemoradiotherapy Improves Outcomes in Advanced Rectal Cancer
As in many areas of medicine, standards of care sometimes precede the actual evidence proving their value. In order to prove the value of preoperative radiotherapy with preoperative chemotherapy in patients with rectal cancer whose tumors are too large for surgery, Norwegian researchers conducted a phase III study. Do the preoperative treatments help make these tumors resectable or can patients be similarly helped without the additional cytotoxic treatment? The results confirmed that the standard of care, in this case, is on target.
Two hundred seven patients with T4 primary rectal tumors or local recurrent tumors were enrolled in the randomized investigation. In total, 98 patients were assigned to receive 50 Gy of preoperative radiotherapy and preoperative fluorouracil and leucovorin chemotherapy, in addition to 16 weeks of chemotherapy postsurgery, and 109 patients received 50 Gy of radiotherapy alone preoperatively, along with postoperative chemotherapy.
More patients in the combined therapy group underwent an R0 resection than in the radiotherapy group alone (84% vs 68%, respectively). A complete pathologic response was noted by the researchers in 16% of those receiving combined therapy compared with 7% given radiotherapy only. The Table illustrates some of the key outcomes measures.
In terms of side effects, the chemotherapy group experienced significantly more grade 3 or 4 toxicities (29% in the preoperative chemotherapy radiotherapy group vs 6% in the preoperative radiotherapy group).
The investigators concluded that the use of preoperative radiotherapy and concurrent chemotherapy resulted in better efficacy and improved outcomes for patients with initially nonresectable rectal tumors than for patients without preoperative chemotherapy treatment.
Braendengen M, Tveit KM, Berglund A, et al. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer.
J Clin Oncol. 2008;26:3687-3694.
JapanDoes CD55 Expression Have Prognostic Significance in Breast Cancer?
A breast cancer cell line that possesses a relatively high percentage of CD55 gene expression was found in vitro to be resistant to aptosis compared with cells that demonstrated less CD55 expression. Researchers from Osaka University and Kansai Medical University, Japan, sought to determine if tumors with high CD55 expression had worse prognosis in vivo.
Using an immunodeficient mouse model, the researchers injected breast cancer cell lines with low (≤1% of tumor cells) and high expression (>1% of tumor cells) of CD55 genes. They subsequently examined clinical samples from 74 mice with breast cancer.
The scientists noted that of breast cancer tumors sampled, 50 (67%) were revealed to express CD55-high cells. In these samples, tumor volume was greater than in mice with CD55-low expressing cells. They believe that CD55 expression may be directly linked to cells’ ability to organize into tumors (i.e., tumorigenic potential). In studying mice in which the tumors were removed, the investigators also found that the CD55-high tumors were more likely to relapse than the CD55- low tumors (P
Although these findings need to be confirmed in humans, they believe that CD55 expression, even by small proportions of cells, has an effect on prognosis in breast cancer.
Ikeda J, Morii E, Liu Y, et al. Prognostic significance of CD55 expression in breast cancer.
Clin Cancer Res. 2008;14:4780-4786.
SwitzerlandTreating Advanced Pancreatic Cancer with Gemcitabine and Capecitabine
Options are few for patients with metastatic pancreatic cancer, although gemcitabine has been shown to delay disease progression somewhat. Swiss oncologists considered the use of capecitabine in combination with gemcitabine in an attempt to obtain a survival benefit.
In this phase III study, 319 patients were randomized to receive either oral capecitabine 650 mg/m2
bid for 14 consecutive days plus infused gemcitabine 1 g/m2
on the first and eighth day of a continuing 3-week cycle or infused gemcitabine 1 g/ m2
once weekly for seven weeks, then once weekly for three weeks of a cycle lasting four weeks. The latter regimen was continued for a maximum of 24 weeks (or until disease advanced).
Nineteen percent of those receiving the combination and 20% receiving gemcitabine alone experienced a clinical benefit response, according to the physicians. The response lasted for 9.5 weeks in the combined therapy group compared with 6.5 weeks in the monotherapy group (P
The investigators assessed patient quality of life, finding that patients did not rate their quality of life differently by assigned treatment. However, quality of life ratings improved in both groups of patients for a short time.
They concluded that oral capecitabine added to gemcitabine provided only limited benefit (duration of clinical response) compared with gemcitabine monotherapy.