Surgery News - October 2007 - (Page 23)

OCTOBER 2007 • SURGERY NEWS ONCOLOGY Early PET Predictive in Barrett-Related Cancer BY BRUCE JANCIN Else vier Global Medical Ne ws C O L O R A D O S P R I N G S — The early metabolic response to induction chemotherapy as assessed by fluorodeoxyglucose-PET just 2 weeks into the treatment of patients with locally advanced Barrett cancer reliably distinguishes those who will have low recurrence and favorable long-term survival post resection from those with a poor prognosis, Dr. Joerg R. Siewert said at the annual meeting of the American Surgical Association. “This suggests FDG-PET can be used to tailor treatment according to the chemosensitivity of tumors. Early response evaluation after induction chemotherapy opens the door to a more individualized therapy in Barrett’s cancer,” added Dr. Siewert, professor and chairman of surgery at Technical University of Munich. Patients without a metabolic response after the first 2 weeks can be spared the morbidity and expense of the remaining 10 weeks of chemotherapy, since they are unlikely to benefit from it, he said. Dr. Siewert reported on 104 patients with locally advanced adenocarcinoma of the esophagus or esophagogastric junction who had a baseline FDG-PET and then were placed on induction chemotherapy before planned tumor resection. After 2 weeks of chemotherapy they had a second FDG-PET, at which point 48% were classified as responders based on at least a 35% reduction in tumor metabolic activity. Responders continued on chemotherapy for 10 more weeks before resection, whereas nonresponders stopped chemotherapy and had palliative surgery based on prior studies indicating that further chemotherapy would be of little benefit. Curative R0 resection was achieved in 96% of responders and 74% of nonresponders. Overall, 20% of responders and 62% of nonresponders had lymph node involvement. Of early metabolic responders, 58% had major histologic remission after resection, as did none of the nonresponders. The distant recurrence rate was 16% in responders and 29% in nonresponders. Me- dian overall survival was more than 5 years in responders and less than 26 months in nonresponders. Induction chemotherapy did not adversely affect surgical risk. Postoperative complications occurred in 34% of patients and in-hospital mortality in 2%, with similar rates in the two groups. The superior survival in the PET-defined early responders is probably due to their more radical resectability and more favorable lymph node–based tumor staging, Dr. Siewert said. Discussant Dr. Murray F. Brennan, chairman of surgery at Memorial Sloan- Kettering Cancer Center, New York, and an ACS Fellow, noted that the patients in Dr. Siewert’s study were classified as AEG I/II. In Dr. Brennan’s own work with AEG III patients having subcardial gastric cancer, he has been unable to show any prognostic significance for an early metabolic response at 2 weeks. Instead, he sees a prognostic value only when FDG-PET is done after 30 days of chemotherapy and at a threshold of at least a 50% reduction in tumor metabolic activity. Dr. Siewert replied that he, too, has observed a big dif- ference in the early prognostic value of PET between AEG I/II and III patients. When audience members asked how he manages the early PET nonresponders, Dr. Siewert said,“For the moment, I think the best treatment option for the nonresponders is still palliative surgical resection, but we have to wait for further trials to make definitive statements.” All papers presented at the 127th annual meeting of the ASA are subsequently submitted to the Annals of Surgery for consideration. ■ INDEX OF ADVERTISERS The Chatham Institute/Wyeth Pharmaceuticals Inc. CME 21 CryoLife Inc. BioGlue Ethicon Endo-Surgery, Inc. Echelon 45 General Scientific Corporation SurgiCam I-Flow Corporation ON-Q Painbuster KCI V.A.C. Kimberly-Clark Worldwide, Inc. InteguSeal Nashville Surgical Instruments Kumar PRE-VIEW Tissue Science Laboratories, Inc. Permacol Karl Storz Endoscopy-America, Inc. Corporate Wyeth Pharmaceuticals Inc. TYGACIL 11-12 2 7 5 15 9 6 13 10 23-24 TYGACIL® (tigecycline) Brief Summary See package insert for full Prescribing Information. For further product information and current package insert, please visit www.wyeth.com or call our medical communications department toll-free at 1-800-934-5556. CONTRAINDICATIONS TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline. WARNINGS Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including tigecycline, and may be life-threatening. Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics and may have similar adverse effects. TYGACIL should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics. TYGACIL may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking tigecycline, the patient should be apprised of the potential hazard to the fetus. Results of animal studies indicate that tigecycline crosses the placenta and is found in fetal tissues. Decreased fetal weights in rats and rabbits (with associated delays in ossification) and fetal loss in rabbits have been observed with tigecycline. (See PRECAUTIONS, Pregnancy.) The use of TYGACIL during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). Results of studies in rats with TYGACIL have shown bone discoloration. TYGACIL should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TYGACIL, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. PRECAUTIONS General Caution should be exercised when considering TYGACIL monotherapy in patients with complicated intra-abdominal infections (cIAI) secondary to clinically apparent intestinal perforation. (See ADVERSE REACTIONS.) In Phase 3 cIAI studies (n=1642), 6 patients treated with TYGACIL and 2 patients treated with imipenem/cilastatin presented with intestinal perforations and developed sepsis/septic shock. The 6 patients treated with TYGACIL had higher APACHE II scores (median = 13) vs the 2 patients treated with imipenem/cilastatin (APACHE II scores = 4 and 6). Due to differences in baseline APACHE II scores between treatment groups and small overall numbers, the relationship of this outcome to treatment cannot be established. Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of TYGACIL. The safety and efficacy of TYGACIL in patients with hospital acquired pneumonia have not been established. In a study of patients with hospital acquired pneumonia, patients were randomized to receive TYGACIL (100 mg initially, then 50 mg every 12 hours) or a comparator. In addition, patients were allowed to receive specified adjunctive therapies. The sub-group of patients with ventilator-associated pneumonia who received TYGACIL had lower cure rates (47.9% versus 70.1% for the clinically evaluable population) and greater mortality (25/131 [19.1%] versus 15/122 [12.3%]) than the comparator. As with other antibacterial drugs, use of TYGACIL may result in overgrowth of non-susceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken. Prescribing TYGACIL in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Information for Patients Patients should be counseled that antibacterial drugs including TYGACIL should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When TYGACIL is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by TYGACIL or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. I

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Surgery News - October 2007

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