S3-Guideline “Exocrine Pancreatic Carcinoma” 20071 ... - DGVS

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468 Leitlinie Comments Several studies, mostly phase-II, show the efficacy of second line therapy for metastatic pancreatic carcinoma with respect to tumor response. Treatments with 5-FU, capecitabine, or raltitrexed, also in combination with oxaliplatin, docetaxel, or irinotecan are possible [229 – 235]. Palliative therapy algorithms Recommendation Palliative chemotherapy should be started with gemcitabine. Recommendation grade: B, evidence level 5, strong consensus Comment There are no studies that investigate the sequential palliative therapy of pancreatic carcinoma. It is recommended to start treatment with gemcitabine. An alternative for metastatic pancreatic carcinoma is a combination of gemcitabine and erlotinib. For patients with locally advanced, inoperable tumors and very good performance-status a combination of gemcitabine with a platinum analogue or capecitabine is possible (see above). Recommendation Standard practice is continuous treatment until progression. Recommendation grade: C, evidence level 5, strong consensus Comment So far, this problem has not been formally investigated. The current data available do not yet allow a change of the present practice of continuous therapy. Clinical efficacy of chemotherapy Recommendation Remission behavior, clinical benefit, or a combination of both are used to evaluate the clinical efficacy. Recommendation grade: A, evidence level 1b, strong consensus Comment These parameters are based on standard clinical practice which is supported by phase-II studies [204]. Palliative radiation therapy Recommendation Indications for palliative radiation therapy are limited to symptomatic metastases (especially skeletal and cerebral metastases). Recommendation grade: A, evidence level 1, strong consensus Radiation therapy alone of a locally advanced, inoperable pancreatic tumor is not indicated. Recommendation grade: B, evidence level 2a, strong consensus [236] Radiochemotherapy for locally advanced, inoperable tumors Recommendation If radiation therapy is performed for locally advanced, inoperable pancreatic carcinoma, radiochemotherapy should be done. Recommendation grade: B, evidence level 2b, consensus Comment In several (mostly older) studies radiochemotherapy is better than radiation therapy alone for locally advanced, inoperable pancreatic carcinoma [237 –241]. However, the data are inconsistent. Adler G et al. S3-Guideline “Exocrine Pancreatic… Z Gastroenterol 2008; 46: 449–482 Recommendations Radiochemotherapy is currently not standard for locally advanced, inoperable pancreatic carcinoma. It may benefit patients with questionable resectable pancreatic carcinoma. Consensus In 5 randomized radiochemotherapy studies (randomized phase- II-studies) a median survival of 10.3 and 13.2 months was reported [242–246]. Recommendation grade: C, evidence level 3 Comparable survival times of 8.7 to 11.7 months were reported for locally advanced, inoperable pancreatic carcinoma in 4 randomized phase-III-studies on chemotherapy [206, 207, 210, 247]. Recommendation grade: B, evidence level 2b, consensus Comment Older randomized phase-II-studies [239, 242], which directly compare radiochemotherapy and chemotherapy show no difference or a small advantage of radiochemotherapy. A recent abstract of a phase-III study shows a slight disadvantage of radiochemotherapy [248]. The current Cochrane-review reports that a better survival can be reached with radiochemotherapy compared to the best supportive therapy or radiation therapy alone. However, radiochemotherapy is associated with higher toxicity. The review concludes that currently there is not enough evidence to recommend radiochemotherapy as a better alternative to chemotherapy alone for patients with locally advanced, inoperable pancreatic carcinoma [203]. Problematic for the radiochemotherapy concept is the fast development of metastases of some patients with pancreatic carcinoma. This is taken into consideration by a concept of the French GERCOR-group. A retrospective analysis showed that patients with locally advanced, inoperable pancreatic carcinoma who do not progress after 3 months of chemotherapy with respect to metastases benefit more from radiochemotherapy that is subsequently performed than from chemotherapy alone [249]. This concept should be tested in a prospective study. Recommendation Radiochemotherapy is not indicated for metastastic pancreatic carcinoma. Recommendation grade: B, evidence level 4, strong consensus If radiochemotherapy is performed for locally advanced, inoperable pancreatic carcinoma, it should be conventionally fractionated and three-dimensionally planned (single dose 1.8 – 2 Gy; total dose 50 – 54 Gy) so as not to increase the toxicity [243–246]. Recommendation grade: C, evidence level 3, consensus Recommendation Surgery should be considered after pertinent staging (if necessary also by laparoscopy) if there is a clear response of the locally advanced pancreatic tumor to radiochemotherapy and if potential resectability is reached. Recommendation grade: C, evidence level 3, consensus Comment A secondary resectability can be reached in about 10% of patients who have undergone RCT [250]. Recommendation If radiochemotherapy is performed outside of clinical trials, it should be done with infusional 5-FU. Recommendation grade: B, evidence level 3, consensus Downloaded by: Thieme Verlagsgruppe. Copyrighted material.
Comment The largest amount of data are available for continuous infusion of the radiosensitizer 5-FU [243, 244, 246, 251, 252]. It has an acceptable side effect profile. Recommendation A combination of 5-FU/mitomycin C during radiochemotherapy should not be used outside of clinical trials because of increased hematologic toxicity [241, 253]. Recommendation grade: A, evidence level 2b, consensus Gemcitabine or a combination of gemcitabine and cisplatin should also not be used outside of clinical trials because of increased toxicity [245, 246, 254–257]. Recommendation grade: B, evidence level 3, consensus Importance of targeted-therapy approaches Recommendation Molecular therapy strategies such as marimastat (recommendation grade: A, evidence level 1), tanomastat (recommendation grade: A, evidence level 1), tipifarnib (recommendation grade: A, evidence level 1), and cetuximab (recommendation grade: C, evidence level 3) currently do not play a role in the palliative therapy of pancreatic cancer [210, 222, 258–260]. Consensus Intra-arterial chemotherapy Recommendation Intra-arterial chemotherapy does not play a role in palliative treatment of pancreatic carcinomas [261, 262]. Recommendation grade: B, evidence level 4, strong consensus Immunotherapeutic/gene therapeutic approaches Recommendation E Immunotherapeutic or gene therapeutic approaches Recommendation grade: C, evidence level 2b, consensus. E or hyperthermia € radiation therapy/radiochemo- or chemotherapy Recommendation grade: C, evidence level 4, consensus. currently do not play a role in palliative treatment of pancreatic carcinomas. Comment These therapeutic approaches are currently experimental and should not be used outside of clinical trials, because insufficient study data are available [263]. Radiofrequency thermoablation Recommendation Radiofrequency thermoablation does not play a role in the palliative treatment of pancreatic carcinomas. Recommendation grade: B, evidence level 5, strong consensus Topic 6: Supportive therapy and follow-up ! Pain therapy Recommendations The standard rules for tumor pain therapy apply for the treatment of pain in patients with pancreatic carcinoma. The WHO’s pain ladder is suitable for pain therapy of pancreatic carcinoma. Other procedures against pain are currently not available [264 – 266]. Leitlinie 469 It should be taken into account that the severity and the development of pain during pancreatic carcinoma can depend on the diet. The treatment procedure should be adapted accordingly (possible additional dose). Invasive neuroablative procedures (especially celiac blockade) also play a role in pancreatic carcinoma [267–269]. Recommendation grade: B, evidence level 3, strong consensus Recommendation There are no specific criteria that influence the drug selection for pancreatic tumor pain therapy. This is true for non-opioids (NSAR, COXIBE, metamizol, paracetamol). Recommendation grade: D, evidence level: 4 This recommendation also applies to the use and selection of opioids. There is no evidence of superiority of certain substances. Recommendation grade: A, evidence level 1b, strong consensus Comments Two reviews of studies on tumor pain treatment concluded that a meta-analysis is not possible for methodologic reasons. This is due to the heterogeneity of the methods and the completely different tools that were used to evaluate the results. Based on these restricted data, NSAR was superior to placebo. Only in a few studies the combination of NSAR and opioids was slightly better than each drug alone. Nonetheless, the difference was significant [270, 271]. Recommendation A certain application route (oral or transdermal) for opioids should not be preferred for pancreatic carcinoma. Possible gastrointestinal problems, especially constipation, which can be caused by motility disorders must be taken into account [272, 273]. Recommendation grade: D, evidence level 3, consensus Recommendation Adjuvants should be used according to the WHO-pain ladder. There are no specific recommendations for the use of adjuvants such as anti-emetica for pancreatic carcinoma [268, 274]. Recommendation grade: B, evidence level 3, strong consensus Recommendation Invasive treatment methods (preferably subcutaneous or intravenous application of opioids, if necessary application near the spine) can be indicated if pain cannot be sufficiently controlled using the WHO-pain ladder [275]. Recommendation grade: D, evidence level 3, strong consensus Recommendation Celiac blockade can principally be indicated for pancreatic carcinoma in some patients [276]. Recommendation grade: C, evidence level 1b, strong consensus Comments There is a meta-analysis on the topic of celiac blockade which takes 59 publications into account [277]. However, only 24 report on 2 or more patients. Thus, more than half are case studies. 21 have retrospective character. 63% use a celiac blockade for pancreatic carcinoma. The methods used were definitely not in line with present standards in all cases. In 32% no radiologic control of the alcohol application was done. Only 2 studies that were taken into account dealt with pain quality. The pain characteristics were also not considered. In summary, in 70 – 90% it Adler G et al. S3-Guideline “Exocrine Pancreatic… Z Gastroenterol 2008; 46: 449–482 Downloaded by: Thieme Verlagsgruppe. Copyrighted material.
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S3-Guideline “Exocrine Pancreatic Carcinoma” 20071 ... - DGVS

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