ABSTRACT: BackgroundThe optimal use of radical surgery to palliate primary rectal cancers presenting with synchronous distant metastases is poorly
defined. We have reviewed stage IV rectal cancer patients to evaluate the effectiveness of radical surgery without radiation
as local therapy.
MethodsEighty stage IV patients with resectable primary rectal tumors treated with radical rectal surgery without radiotherapy were
identified. Sixty-one (76%) patients received chemotherapy; response information was available for 34 patients.
ResultsRadical resection was accomplished by low anterior resection (n=65), abdominoperineal resection (n=11), and Hartmann’s resection
(n=4). Surgical complications were seen in 12 patients (15%), with 1 death and 4 reoperations. The local recurrence rate was
6% (n=5), with a median time to local recurrence of 14 months. Only one patient received pelvic radiotherapy as salvage treatment.
One patient required subsequent diverting colostomy. Median survival was 25 months. On multivariate analysis, the extent of
metastasis and response to chemotherapy were determinants of prolonged survival.
ConclusionsFor patients who present with distant metastases and resectable primary rectal cancers, radical surgery without radiotherapy
can provide durable local control with acceptable morbidity. The extent of metastatic disease and the response to chemotherapy
are the major determinants of survival. Effective systemic chemotherapy should be given high priority in the treatment of
stage IV rectal cancer.
Annals of Surgical Oncology 04/2012; 9(10):954-960. · 4.17 Impact Factor
ABSTRACT: Objectives: To determine the maximum tolerated dose (MTD), toxicities, and suitable dose for weekly 1-h paclitaxel combined with weekly
cisplatin and irinotecan to treat advanced gastrointestinal malignancies. Methods: Thirty patients with metastatic or locally advanced (unresectable or recurrent) gastrointestinal solid tumors were enrolled
on this single-center, phase I study. Patients were treated with paclitaxel given over 1h at 1 of 4 dose levels (40, 50, 65,
or 80 mg/m2). Paclitaxel was followed by fixed doses of cisplatin (30 mg/m2) and irinotecan (50 mg/m2). All treatment was administered sequentially, once a week, in 6-week cycles (4 weeks on, 2 weeks off). Dose-limiting toxicity
(DLT) was defined as a 2-week delay in treatment for grade 3 or 4 non-hematologic toxicity, neutropenic fever, a 1-week delay
for grade 4 hematologic toxicity, or a 2-week delay for grade 3 hematologic toxicity. Results: Thirty patients were recruited; 28 patients were assessable for safety. Most of the patients (70%) had no prior chemotherapy.
The primary first-cycle DLTs were neutropenia, diarrhea, and nausea. Paclitaxel at 65 mg/m2 was defined as the MTD. The most common grade 3–4 toxicities observed during all cycles were neutropenia (57%), febrile neutropenia
(11%), diarrhea (29%), fatigue (29%), and nausea (18%). No patients had G-CSF (Neupogen, Amgen Inc., Thousand Oaks, CA) support.
Responses were observed in gastric, esophageal, and pancreatic cancers. Conclusion: Paclitaxel at 65 mg/m2, cisplatin (30 mg/m2), and irinotecan (50 mg/m2) given weekly can be safely administered to patients with solid tumor malignancies. To improve cumulative toxicities, a schedule
modification was required (3-week cycle; 2-on, 1-off) Neutropenia was the most common DLT. This combination showed substantial
activity, particularly in patients with gastric and esophageal adenocarcinoma, and phase II evaluation could be considered.
Investigational New Drugs 04/2012; 27(4):366-373. · 3.36 Impact Factor
Journal of Gastrointestinal Cancer 04/2012; 43(1):93-96.
ABSTRACT: BackgroundWe sought to determine the response rate and toxicity profile of sequential paclitaxel and bryostatin-1, a novel, selective
inhibitor of protein kinase C, in patients with advanced esophageal cancer.
Patients and methodsPatients with advanced esophageal and gastroesophageal junction cancer were enrolled. All gave informed consent. They were
initially treated with paclitaxel 90mg/m2 intravenously on Day 1 and bryostatin-1 50μg/m2 on Day 2 weekly for three consecutive weeks out of four. Because of severe myalgias, dosing was reduced to paclitaxel 80mg/m2 with bryostatin-1 40μg/m2 and then to paclitaxel 80mg/m2 with bryostatin-1 25μg/m2.
ResultsTwenty-four patients were enrolled, with 22 assessable for response. The partial response rate was 27%. 10 patients treated
with bryostatin-1 40–50μg/m2 had a response rate of 40 versus 17% at bryostatin-1 25μg/m2 (p-value=0.3). Median time-to-progression was 3.7months and median survival was 8.3months. Grade 3/4 myalgias were seen
in 50% of patients. Myalgias appeared to be related to bryostatin-1 dose. Because of toxicity, the trial was closed prior
to full accrual.
ConclusionsDespite potential anti-tumor activity of this combination in patients with advanced esophageal cancer, further development
is not warranted, given the severe toxicity, especially myalgias, that were seen.
Cancer Chemotherapy and Pharmacology 09/2008; 62(5):875-880. · 2.83 Impact Factor