MEDLINE Abstracts: Combined Modality Therapy for Pancreatic Cancer
Coquard R, Ayzac L, Gilly FN, Romestaing P, Ardiet JM, Sondaz C, Sotton MP, Sentenac I, Braillon G, Gerard JP
Radiotherapy & Oncology 44(3):271-5, 1997 Sep
Background and Purpose: To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection.
Materials and Methods: From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients.
Results: The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early postoperative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months.
Conclusion: IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma.
Noble S, Goa KL
Drugs 54(3):447-72, 1997 Sep
Gemcitabine [2'-deoxy-2',2'-difluorocytidine monohydrochloride (beta isomer); dFdC] is a novel deoxycytidine analogue which was originally investigated for its antiviral effects but has since been developed as an anticancer therapy. Gemcitabine monotherapy produced an objective tumour response in 18 to 26% of patients with advanced non-small cell lung cancer (NSCLC) and appears to have similar efficacy to cisplatin plus etoposide. Objective response rates ranging from 26 to 54% were recorded when gemcitabine was combined with cisplatin, and 1-year survival duration after such treatment ranged from 35 to 61%. Improvements in a range of NSCLC disease symptoms and/or in general performance status occurred in many patients who received gemcitabine, with or without cisplatin, in 3 clinical trials. Gemcitabine appears to be cost effective compared with best supportive care for NSCLC. In addition, direct costs associated with administration of gemcitabine monotherapy may be lower than those for some other NSCLC chemotherapy options, according to retrospective cost-minimisation analyses. The combination of gemcitabine plus cisplatin was associated with a lower cost per tumour response than cisplatin plus etoposide or cisplatin plus vinorelbine, according to a retrospective cost-effectiveness analysis. In a single comparative study in patients with advanced pancreatic cancer, gemcitabine was more effective than fluorouracil with respect to survival duration and general clinical status. It also showed modest antitumour and palliative efficacy in patients refractory to fluorouracil. Gemcitabine appears to be well tolerated, although further comparisons with other chemotherapy regimens are required. The available data indicate that gemcitabine monotherapy is better tolerated than cisplatin plus etoposide in patients with NSCLC. Data from noncomparative studies suggest that the combination of gemcitabine and cisplatin has an acceptable tolerabilty profile. In a single trial in patients with pancreatic cancer, fluorouracil was better tolerated than gemcitabine; however, gemcitabine was generally well tolerated overall in this study. Thus, gemcitabine (with or without cisplatin) may prove attractive to patients with advanced NSCLC, given their limited life expectancy and the toxicity associated with many other chemotherapy regimens. More detailed characterisation of its risk-benefit profile compared with those of current and developing regimens for NSCLC should be possible once results from several ongoing studies are available. Gemcitabine is a valuable new chemotherapy option for patients with advanced pancreatic cancer, a disease considered incurable at present. Its apparent survival and palliative benefits over fluorouracil require confirmation, but are encouraging, as the need to improve both the duration and quality of survival in these patients is well recognised.
Dobelbower RR, Merrick HW, Khuder S, Battle JA, Herron LM, Pawlicki T
International Journal of Radiation Oncology, Biology, Physics 39(1):31-7, 1997 Aug 1
Purpose: A retrospective analysis to determine differences in survival of patients with pancreatic adenocarcinoma treated by radical surgery with and without adjuvant radiation therapy.
Methods and Materials: Between 1980 and 1995, 249 patients with pancreatic tumors were identified at the Medical College of Ohio. Forty-four of these patients underwent radical surgical procedures with curative intent. These patients were divided into four groups according to treatment: surgery alone (n = 14), surgery plus intraoperative radiation therapy (IORT) (n = 6), surgery plus external beam radiation therapy (EBRT) (n = 14), or surgery plus both IORT and EBRT (n = 10). Outcome and survival were analyzed among the four groups.
Results: The median survival time of patients treated with radical surgery alone was 6.5 months. The median survival time for the surgery plus IORT group was 9 months; however, 33.3% (two of six) of these patients survived longer than 5 years. This survival pattern was borderline significantly better than that for the surgery alone group (p = 0.0765). The surgery plus EBRT and the surgery plus IORT and EBRT groups had median survival times of 14.5 and 17.5 months, respectively. These were significantly better than that of the surgery alone group (p = 0.0004 and p = 0.0002, respectively). The addition of radiation therapy did not affect the treatment complication rate.
Conclusion: The survival of patients who were treated with radical surgery alone was significantly poorer than that of patients who received adjuvant radiation therapy. These results are consistent with other studies in the literature. Patients treated with all three modalities (surgery, IORT, and EBRT) displayed the best median survival time.
Lygidakis NJ, Dedemati G, Spenzaris N, Theodoropoulou M
Hepato-Gastroenterology 44(16):1222-8, 1997 Jul-Aug
Background/Aims: The aim of this study was to evaluate the combination of immunochemotherapy and stop-flow upper abdominal chemotherapy in the prolongation of survival in patients with unresectable pancreatic cancer.
Methodology: Thirty unresectable pancreatic cancer patients were treated with immuno-chemotherapy in combination with stop-flow upper abdominal chemotherapy, in an attempt to improve survival time.
Results: The results obtained in this study indicate that this kind of treatment is feasible, safe and effective for patients suffering from Stage III and IV pancreatic duct carcinoma. Twenty per cent of the patients within this group were able to undergo radical resection and remain alive and free of disease, with a mean survival rate of 16 months.
Conclusion: The multi-modality approach used in this study achieved promising results for pancreatic cancer patients and is recommended as a promising therapeutic alternative.
Awad SS, Colletti L, Mulholland M, Knol J, Rothman ED, Scheiman J, Eckhauser FE
American Surgeon 63(7):634-8, 1997 Jul
Few patients with pancreatic cancer have resectable disease at the time of diagnosis, and a variety of nonsurgical techniques are available to provide effective palliation of jaundice and pain. Accurate preoperative staging is essential to identify patients with unresectable disease, thereby minimizing unnecessary surgery. Currently used diagnostic tests include contrast-enhanced computerized tomography (CT), visceral angiography, endoscopic ultrasound, and laparoscopy, but their utility remains controversial. To evaluate the accuracy of these various diagnostic tests, 30 consecutive patients with histologically proven pancreatic or ampullary adenocarcinoma treated between 1992 and 1996 were evaluated. All 30 patients had contrast-enhanced CT and laparoscopy, 22 patients (73%) had visceral angiography, and 16 patients (53%) had endoscopic ultrasound. Individual and combined predictive values of resectability and unresectability as well as the sensitivities and specificities were determined for all diagnostic tests and compared with intraoperative findings. When CT, visceral angiography, and laparoscopy were combined, the predictive values of resectability and unresectability were 75 and 90 per cent, respectively, with a sensitivity of 75 per cent and a specificity of 90 per cent. Therefore, the combined use of selected diagnostic tests proved more effective than any single diagnostic test for accurately staging patients with pancreatic head and ampullary cancers and should be considered to minimize unnecessary surgery.
Douglass HO
Hepato-Gastroenterology 40(5):433-42, 1993 Oct
For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and 5-fluorouracil has been shown to enhance patient survival. Following pancreatectomy, results in a second group of patients confirmed the benefit of 40 Gy of radiation administered as a split course, combined with 5-fluorouracil during and following the radiation therapy, as noted in the original randomized study of the Gastrointestinal Tumor Study Group. When the disease is locally unresectable, 60 Gy of radiation administered in a double split regimen, in combination with 5-fluorouracil, has significantly prolonged survival. Split courses of radiation therapy seem better tolerated, allowing a greater proportion of patients to complete this phase of treatment. Hyperfractionation, heavy ion irradiation and intraoperative radiation therapy have not been found to be more beneficial. Newer approaches include continuous intravenous or intraarterial infusion of the 5-fluorouracil, addition of mitomycin C or cisplatin. The results of neoadjuvant trials of radiation and chemotherapy are not sufficiently mature to determine their effect on patient survival. Neoadjuvant therapy has not been subjected to testing in randomized trials. Chemotherapy will continue to offer very limited benefit for patients with advanced metastatic disease until more effective drugs can be developed. Innovative approaches utilizing growth factors and photodynamic therapy should be studied in carefully monitored fashion.
Jessup JM, Posner M, Huberman M
Seminars in Surgical Oncology 9(1):27-32, 1993 Jan-Feb
Carcinoma of the pancreas has an especially grim prognosis. Only 1-3% of patients survive for 5 years. Radical pancreaticoduodenectomy, especially for minimal disease, is currently the only chance for cure. While radiation therapy does not improve overall survival, it may improve local control following radical resection and decrease pain in locally advanced cancers. Although chemotherapy has led to significant improvements in survival in patients with locally advanced disease, the overall effect is small. When surgery, radiotherapy, and chemotherapy are administered to localized carcinomas in randomized, prospective trials, survival is significantly lengthened. Similar trials in locally advanced, unresectable pancreatic cancer also confirm the concept of synergistic interaction between therapies. Thus, pancreas carcinoma is one neoplasm where multimodality therapy has had a demonstrable, although small effect.
Coquard R, Ayzac L, Gilly FN, Romestaing P, Ardiet JM, Sondaz C, Sotton MP, Sentenac I, Braillon G, Gerard JP
Radiotherapy & Oncology 44(3):271-5, 1997 Sep
Background and Purpose: To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection.
Materials and Methods: From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients.
Results: The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early postoperative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months.
Conclusion: IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma.
Noble S, Goa KL
Drugs 54(3):447-72, 1997 Sep
Gemcitabine [2'-deoxy-2',2'-difluorocytidine monohydrochloride (beta isomer); dFdC] is a novel deoxycytidine analogue which was originally investigated for its antiviral effects but has since been developed as an anticancer therapy. Gemcitabine monotherapy produced an objective tumour response in 18 to 26% of patients with advanced non-small cell lung cancer (NSCLC) and appears to have similar efficacy to cisplatin plus etoposide. Objective response rates ranging from 26 to 54% were recorded when gemcitabine was combined with cisplatin, and 1-year survival duration after such treatment ranged from 35 to 61%. Improvements in a range of NSCLC disease symptoms and/or in general performance status occurred in many patients who received gemcitabine, with or without cisplatin, in 3 clinical trials. Gemcitabine appears to be cost effective compared with best supportive care for NSCLC. In addition, direct costs associated with administration of gemcitabine monotherapy may be lower than those for some other NSCLC chemotherapy options, according to retrospective cost-minimisation analyses. The combination of gemcitabine plus cisplatin was associated with a lower cost per tumour response than cisplatin plus etoposide or cisplatin plus vinorelbine, according to a retrospective cost-effectiveness analysis. In a single comparative study in patients with advanced pancreatic cancer, gemcitabine was more effective than fluorouracil with respect to survival duration and general clinical status. It also showed modest antitumour and palliative efficacy in patients refractory to fluorouracil. Gemcitabine appears to be well tolerated, although further comparisons with other chemotherapy regimens are required. The available data indicate that gemcitabine monotherapy is better tolerated than cisplatin plus etoposide in patients with NSCLC. Data from noncomparative studies suggest that the combination of gemcitabine and cisplatin has an acceptable tolerabilty profile. In a single trial in patients with pancreatic cancer, fluorouracil was better tolerated than gemcitabine; however, gemcitabine was generally well tolerated overall in this study. Thus, gemcitabine (with or without cisplatin) may prove attractive to patients with advanced NSCLC, given their limited life expectancy and the toxicity associated with many other chemotherapy regimens. More detailed characterisation of its risk-benefit profile compared with those of current and developing regimens for NSCLC should be possible once results from several ongoing studies are available. Gemcitabine is a valuable new chemotherapy option for patients with advanced pancreatic cancer, a disease considered incurable at present. Its apparent survival and palliative benefits over fluorouracil require confirmation, but are encouraging, as the need to improve both the duration and quality of survival in these patients is well recognised.
Dobelbower RR, Merrick HW, Khuder S, Battle JA, Herron LM, Pawlicki T
International Journal of Radiation Oncology, Biology, Physics 39(1):31-7, 1997 Aug 1
Purpose: A retrospective analysis to determine differences in survival of patients with pancreatic adenocarcinoma treated by radical surgery with and without adjuvant radiation therapy.
Methods and Materials: Between 1980 and 1995, 249 patients with pancreatic tumors were identified at the Medical College of Ohio. Forty-four of these patients underwent radical surgical procedures with curative intent. These patients were divided into four groups according to treatment: surgery alone (n = 14), surgery plus intraoperative radiation therapy (IORT) (n = 6), surgery plus external beam radiation therapy (EBRT) (n = 14), or surgery plus both IORT and EBRT (n = 10). Outcome and survival were analyzed among the four groups.
Results: The median survival time of patients treated with radical surgery alone was 6.5 months. The median survival time for the surgery plus IORT group was 9 months; however, 33.3% (two of six) of these patients survived longer than 5 years. This survival pattern was borderline significantly better than that for the surgery alone group (p = 0.0765). The surgery plus EBRT and the surgery plus IORT and EBRT groups had median survival times of 14.5 and 17.5 months, respectively. These were significantly better than that of the surgery alone group (p = 0.0004 and p = 0.0002, respectively). The addition of radiation therapy did not affect the treatment complication rate.
Conclusion: The survival of patients who were treated with radical surgery alone was significantly poorer than that of patients who received adjuvant radiation therapy. These results are consistent with other studies in the literature. Patients treated with all three modalities (surgery, IORT, and EBRT) displayed the best median survival time.
Lygidakis NJ, Dedemati G, Spenzaris N, Theodoropoulou M
Hepato-Gastroenterology 44(16):1222-8, 1997 Jul-Aug
Background/Aims: The aim of this study was to evaluate the combination of immunochemotherapy and stop-flow upper abdominal chemotherapy in the prolongation of survival in patients with unresectable pancreatic cancer.
Methodology: Thirty unresectable pancreatic cancer patients were treated with immuno-chemotherapy in combination with stop-flow upper abdominal chemotherapy, in an attempt to improve survival time.
Results: The results obtained in this study indicate that this kind of treatment is feasible, safe and effective for patients suffering from Stage III and IV pancreatic duct carcinoma. Twenty per cent of the patients within this group were able to undergo radical resection and remain alive and free of disease, with a mean survival rate of 16 months.
Conclusion: The multi-modality approach used in this study achieved promising results for pancreatic cancer patients and is recommended as a promising therapeutic alternative.
Awad SS, Colletti L, Mulholland M, Knol J, Rothman ED, Scheiman J, Eckhauser FE
American Surgeon 63(7):634-8, 1997 Jul
Few patients with pancreatic cancer have resectable disease at the time of diagnosis, and a variety of nonsurgical techniques are available to provide effective palliation of jaundice and pain. Accurate preoperative staging is essential to identify patients with unresectable disease, thereby minimizing unnecessary surgery. Currently used diagnostic tests include contrast-enhanced computerized tomography (CT), visceral angiography, endoscopic ultrasound, and laparoscopy, but their utility remains controversial. To evaluate the accuracy of these various diagnostic tests, 30 consecutive patients with histologically proven pancreatic or ampullary adenocarcinoma treated between 1992 and 1996 were evaluated. All 30 patients had contrast-enhanced CT and laparoscopy, 22 patients (73%) had visceral angiography, and 16 patients (53%) had endoscopic ultrasound. Individual and combined predictive values of resectability and unresectability as well as the sensitivities and specificities were determined for all diagnostic tests and compared with intraoperative findings. When CT, visceral angiography, and laparoscopy were combined, the predictive values of resectability and unresectability were 75 and 90 per cent, respectively, with a sensitivity of 75 per cent and a specificity of 90 per cent. Therefore, the combined use of selected diagnostic tests proved more effective than any single diagnostic test for accurately staging patients with pancreatic head and ampullary cancers and should be considered to minimize unnecessary surgery.
Douglass HO
Hepato-Gastroenterology 40(5):433-42, 1993 Oct
For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and 5-fluorouracil has been shown to enhance patient survival. Following pancreatectomy, results in a second group of patients confirmed the benefit of 40 Gy of radiation administered as a split course, combined with 5-fluorouracil during and following the radiation therapy, as noted in the original randomized study of the Gastrointestinal Tumor Study Group. When the disease is locally unresectable, 60 Gy of radiation administered in a double split regimen, in combination with 5-fluorouracil, has significantly prolonged survival. Split courses of radiation therapy seem better tolerated, allowing a greater proportion of patients to complete this phase of treatment. Hyperfractionation, heavy ion irradiation and intraoperative radiation therapy have not been found to be more beneficial. Newer approaches include continuous intravenous or intraarterial infusion of the 5-fluorouracil, addition of mitomycin C or cisplatin. The results of neoadjuvant trials of radiation and chemotherapy are not sufficiently mature to determine their effect on patient survival. Neoadjuvant therapy has not been subjected to testing in randomized trials. Chemotherapy will continue to offer very limited benefit for patients with advanced metastatic disease until more effective drugs can be developed. Innovative approaches utilizing growth factors and photodynamic therapy should be studied in carefully monitored fashion.
Jessup JM, Posner M, Huberman M
Seminars in Surgical Oncology 9(1):27-32, 1993 Jan-Feb
Carcinoma of the pancreas has an especially grim prognosis. Only 1-3% of patients survive for 5 years. Radical pancreaticoduodenectomy, especially for minimal disease, is currently the only chance for cure. While radiation therapy does not improve overall survival, it may improve local control following radical resection and decrease pain in locally advanced cancers. Although chemotherapy has led to significant improvements in survival in patients with locally advanced disease, the overall effect is small. When surgery, radiotherapy, and chemotherapy are administered to localized carcinomas in randomized, prospective trials, survival is significantly lengthened. Similar trials in locally advanced, unresectable pancreatic cancer also confirm the concept of synergistic interaction between therapies. Thus, pancreas carcinoma is one neoplasm where multimodality therapy has had a demonstrable, although small effect.
SHARE
![Pediatric Supportive Care (PDQ®): Supportive care - Patient Information [NCI]-Overview](https://cdnus.oss-us-west-1.aliyuncs.com/libs/images/NewsJpg/cate_6/072_215x160.jpg)
