Two doses of NGR-hTNF in combination with capecitabine plus oxaliplatin in colorectal cancer patients failing standard therapies.

BACKGROUND: asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF), an agent selectively damaging the tumour vasculature, showed a biphasic dose-response curve in preclinical models. Previous phase I trials of NGR-hTNF indicated 0.8 and 45 µg/m(2) as optimal biological and maximum-tolerated dose, respectively. PATIENTS AND METHODS: Two sequential cohorts of 12 colorectal cancer (CRC) patients who had failed standard therapies received NGR-hTNF 0.8 or 45 µg/m(2) in combination with capecitabine-oxaliplatin (XELOX). RESULTS: Median number of prior treatment lines was 3 in the low-dose and 2 in the high-dose cohort. Overall, 21 patients had been pretreated with oxaliplatin-based regimens. No grade 3-4 NGR-hTNF-related toxicities were observed. Grade 1-2 chills were reported in 43% and 40% of cycles in the low-dose and high-dose cohorts, respectively. In the low-dose cohort, one patient achieved a partial response and five had stable disease for a median of 4.6 months. In the high-dose cohort, six patients had stable disease for a median of 3.6 months. Three-month progression-free survival (PFS) rates were 50% and 33% in the low-dose and high-dose cohort, respectively. Three patients in low-dose cohort experienced PFS longer than PFS on last prior therapy. CONCLUSIONS: Both NGR-hTNF doses were safely combined with XELOX in pretreated CRC patients. Hint of activity was apparent only with low-dose NGR-hTNF.

First-line single-agent cetuximab in patients with advanced colorectal cancer.

BACKGROUND: The anti-epidermal growth factor receptor (EGFR) antibody cetuximab is active in heavily pretreated patients with metastatic colorectal cancer (mCRC) both in monotherapy and in combination with chemotherapy (CT). This study assesses the antitumor activity of single-agent cetuximab in CT-naive patients. PATIENTS AND METHODS: Phase II clinical trial was used. Patients were EGFR positive by immunohistochemistry and were not candidate for radical surgery, even in the case of substantial tumor shrinkage. Cetuximab was administered weekly. RESULTS: Thirty-nine patients were treated and evaluated. The most common adverse event was skin toxicity (89% any grade; 48% grade 1; 31% grade 2; 10% grade 3). One patient had a complete response and three obtained partial responses (10% overall response rate). Thirteen patients had stable disease (34%). Twenty-two patients experienced progressive disease (56%). Overall median time to progression (TTP) was 2 months, and the responders individual TTP was 12, 9, 9, and 6 months. CONCLUSIONS: Even in chemo-naive patients, cetuximab as single agent is active only in a small fraction of mCRC, similarly to what has been reported for heavily pretreated patients. The extent of benefit when response occurs is, however, such that it is mandatory to intensify the search for the predictive markers of response to cetuximab therapy.

[The results of sandwich adjuvant radiotherapy in 2nd- and 3rd-stage rectal adenocarcinoma. The authors' personal experience]. / Risultati della radioterapia adiuvante a "sandwich" nell'adenocarcinoma del retto negli stadi II e III. Esperienza personale.

From January, 1985, to June, 1993, 125 patients with stages B2-C adenocarcinomas of the rectum were submitted to pre- and postoperative irradiation according to Thomas Jefferson University protocol guidelines. Five hundred cGy were administered as a single preoperative dose 24 hours before surgery using parallel opposed (AP-PA) treatment fields including the whole pelvis. Pathologic samples were classified following the Astler-Coller staging criteria. Forty-seven patients had no postoperative treatment because their disease stage was A, B1 or D, 11 for refused consent and 9 postoperative complications preventing any further therapy. Seventy-eight patients concluded the treatment schedule and are assessable for response. Radiotherapy total dose consisted of 4400-5000 cGy administered over 5-6 weeks: the patients were treated with megavoltage photons (15-MeV photons) and one dose fraction of 2 Gy was delivered daily, 5 days a week, with the "box" or the "three-field" technique. Median follow-up time was 50.2 months from the beginning of treatment for all the patients in our series (range: 18-120 months). Radiation therapy was well tolerated: 5 patients had severe diarrhea and 2 had small bowel obstruction which required surgery. Local recurrences were observed in 13 of 78 patients (16.7%). Overall actuarial survival at 5 years was 66.8%. Our results confirm the efficacy of this treatment, which is in agreement with international literature data. However, no difference was seen relative to the results obtained with postoperative irradiation alone. We conclude that sandwich radiotherapy can be an effective tool for the local control of rectal adenocarcinoma, with acceptable morbidity, even though it fails to prevent metastases.