There had been no trials of Xeloda and Abraxane for pancreatic cancer. The GAX regimen is in a clinical trial: Nab-paclitaxel (Abraxane), Gemcitabine, and Capecitabine (Xeloda) for Pancreatic Adenocarcinoma, NCT01161186. The purpose of this study is to evaluate optimal dose and safety of the combination of Abraxane, gemcitabine, and Xeloda (capecitabine) (AGX) as first-line therapy in patients with metastatic pancreatic cancer. The trial was completed and awaits publication.

.

David B. Smith et al, Capecitabine: an evidence-based review of its effectiveness in the treatment of carcinoma of the pancreas, re Evid. 2007; 2(2): 111–119.
Hosein PJ, Pastorini VH, Gomez CM, Macintyre J, Merchan JR, Ferrell A, et al.A phase II trial of nab-paclitaxel (NP) in patients with advanced pancreatic cancer (PC) who have progressed on gemcitabine-based therapy. 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 214.

Von Hoff DD, et al. Promising clinical activity of a NAB paclitaxel plus gemcitabine combination in a disease-specific Phase I trial in patients with advanced pancreatic cancer. 2008 annual meeting of the American Association for Cancer Research. Abstract 4179.

Hosein PJ, Pastorini VH, Gomez CM, Macintyre J, Merchan JR, Ferrell A, et al.A phase II trial of nab-paclitaxel (NP) in patients with advanced pancreatic cancer (PC) who have progressed on gemcitabine-based therapy. 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 214.

For Lay version see here

Currently, identification of teh P16 gene is not clinically significant. All individuals considered at high risk for melanoma should be managed similarly regardless of p16 mutation status. Individuals at increased risk for melanoma should be identified. Family history information should be obtained from all individuals with melanoma or dysplastic nevi, and first-degree relatives should be screened because of the increased risk of CMM in melanoma-prone families in any case. These individuals should be educated about sun protection, avoidance of intense sun exposure, and other preventive measures, such as learning how to detect dysplastic nevi characteristics and melanoma warning signs.

Management recommendations also include examination of the entire skin surface by a skilled healthcare provider every 6 months from 10 years, or earlier for suspicious nevi, until nevi are stable and annually thereafter.

Similarly there are no guidelines that recommend pancreatic cancer screening based on identification of the p 16 mutation.
http://www.moffitt.org/moffittapps/ccj/v4n1/department2.html (Guidelines)

Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004;351:998-1012.

Parker JF, Florell SR, Alexander A, DiSario JA, Shami PJ, Leachman SA.
Pancreatic carcinoma surveillance in patients with familial melanoma. Arch Dermatol. 2003 Aug;139(8):1019-25.

Practice guideline – http://www.cancercare.on.ca/pdf/pebc2-7s.pdf

nccn.org, pancreatic cancer

N. Xiros et al, Carboplatin plus gemcitabine in patients with inoperable or metastatic pancreatic cancer: a phase II multicenter study by the Hellenic Cooperative Oncology Group Annals of Oncology 2005 16(5):773-779;

Patients with advanced pancreatic cancer profit from palliative chemotherapy but the role of second-line chemotherapy is not yet established. Pancreatic cancer affects more than 30,000 people in the United States each year and when the cancer does not respond to standard chemotherapy, additional treatments have not been approved. Research on effectiveness of second line therapy is ongoing; so far it appears that selected patients can benefit form second line chemotherapy but the best regimens and how to select patients has not been determined.

The evidence for second-line chemotherapy after progression on a gemcitabine-based regimen is scant. The CONKO-003 investigators randomly assigned patients in the second line of chemotherapy to either a regimen of 5-FU, leucovorin, and oxaliplatin (OFF regimen) or best supportive care (BSC). The OFF regimen consisted of folinic acid (200 mg/m²) followed by 5-FU (2 g/m² [24 hours] on days 1, 8, 15, and 22) and oxaliplatin (85 mg/m² on days 8 and 22). After a rest of 3 weeks, the next cycle was started on day 43. The trial was terminated early because of poor accrual, and only 46 patients were randomly assigned to either the OFF regimen or BSC. Median second-line survival was 4.82 months (95% CI, 4.29–5.35) for the OFF-regimen treatment and 2.30 months (95% CI, 1.76–2.83) with BSC alone (HR, 0.45; 95% CI, 0.24–0.83).  Median OS was 9.09 months for the sequence of gemcitabine/5-FU, leucovorin, and oxaliplatin or GEM-OFF and 7.90 months for gemcitabine/best supportive care or GEM-BSC. The early closure of the study and the very small number of patients made the P values misleading. Therefore, second-line chemotherapy with the OFF regimen may be associated with improved survival but requires more study.

NCCN recommends capecitabine, Folfox or CapeOx)XelOx) for second line therapy on p. PANC-G.

Pelzer U, Schwaner I, Stieler J, et al.: Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 47 (11): 1676-81, 2011

A. Mancuso, P. Saletti, S. Sacchetta, E. Romagnani, F. Cavalli and C. N. Sternberg Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 14107

T. Herrmann, D. Jaeger, W. Stremmel, C. Herrmann
Second-line chemotherapy in advanced pancreatic cancer: A retrospective, single-center analysis.Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 15187

There are some special groups in which screening may be reasonable. These include hereditary pancreatitism chronic pancreatitits and thos with a strong family history.

An individual’s risk of developing pancreatic cancer increases with the number of affected first-degree relatives, and it is estimated that hereditary factors account for at least 5% of pancreatic cancers.2 Familial pancreatic cancer (FPC) is inherited in an autosomal dominant manner, with variable penetrance. In order to diagnose FPC, it is necessary to obtain an accurate and thorough family history with particular emphasis on the oncologic history. While it is important to ascertain any family history of pancreatic cancer, it is also important to screen for a personal and family history of extrapancreatic malignancies, and to obtain a family cancer history beyond first-degree relatives, if possible. The family history allows the clinician to determine if prior cases of pancreatic cancer in relatives are more likely to be familial or sporadic.

If a diagnosis of FPC is made in conjunction with a family history of extrapancreatic malignancies, consideration should also be given to a syndromic FPC. Hereditary pancreatic cancer has been associated with colorectal cancer in the Lynch syndrome II variety of hereditary nonpolyposis colorectal cancer (HNPCC), with breast and ovarian cancer (breast–ovarian cancer syndrome), Peutz–Jeghers syndrome, and melanomas in the familial atypical multiple mole melanoma (FAMMM) syndrome. A family history of early pancreatitis suggestive of hereditary pancreatitis is also an important risk factor for subsequent pancreatic adenocarcinoma.

Although there are no consensus guidelines on what defines FPC, an assessment of the risk of developing pancreatic cancer according to the number of affected relatives is useful in clinical practice. Genetic testing might be a useful adjunct in the management of a patient with FPC, but should be performed only after appropriate genetic counseling. Many important genes that have at least a partial role in FPC, both syndrome-associated and nonsyndromic, have been identified. In a multicenter study, 40% of patients with a history of hereditary pancreatitis developed pancreatic adenocarcinoma by 70 years of age.6 Testing for the cationic trypsinogen gene (PRSS1), which is associated with hereditary pancreatitis, is available. The FAMMM syndrome, described in 1975, is associated with a germline mutation of the p16 tumor suppressor gene (CDKN2A). Testing for p16 mutations helps identify those patients at risk for pancreatic malignancy in families with a history of melanomas and pancreatic cancer. The majority of FPC cases, however, are nonsyndromic.

CT scanning, while critical in the management of pancreatic adenocarcinoma, has not proven to be of definitive benefit in screening for pancreatic malignancy in FPC, mainly because of a lack of adequate resolution to detect dysplasia. For CT scanning to exert a benefit in terms of mortality, it must detect either premalignant changes or early malignancy, so that curative surgery can be performed.

In conclusion, genetic counselling should precede radiological screening, an attempt to better define a familial syndrome should be made before screening, and there is no evidence that any screening is supror to another or to no screening at all. There is little evidence for CT scan based screening.

U.S. Preventive Services Task Force (USPSTF). Screening for pancreatic cancer: recommendation statement. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ); 2004 Feb. 3 p. [4 references]

Ulrich CD; Consensus Committees of the European Registry of Hereditary Pancreatic Diseases, Midwest Multi-Center Pancreatic Study Group, International Association of Pancreatology.Pancreatic cancer in hereditary pancreatitis: consensus guidelines for prevention, screening and treatment.Pancreatology. 2001;1(5):416-22
Ellis I, Lerch MM, Whitcomb DC; Consensus Committees of the European Registry of Hereditary Pancreatic Diseases, Midwest Multi-Center Pancreatic Study Group, International Association of Pancreatology.  Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues.
Pancreatology. 2001;1(5):405-15

Rajesh N Keswani, Amy Noffsinger and Irving Waxman A family history of pancreatic cancer, Nature Clinical Practice Gastroenterology & Hepatology (2006) 3, 586-591

Kanjeekal S, Biagi J, Walker-Dilks C. PET imaging in pancreatic cancer: recommendations. Toronto (ON): Cancer Care Ontario (CCO); 2009 Jan 19. 20 p. (Recommendation report – PET; no. 5).  [34 references]

Locally advanced and metastatic pancreatic adenocarcinomas carry a very poor prognosis. In patients treated with the standard palliative treatment gemcitabine (GEM), median survival still remains only 6 months. Over the last several years, many trials have been designed combining GEM with various other drugs to treat chemo-naive patients, with the aim to improve overall survival. Unfortunately, none of the GEM-based combinations studied so far have reached that objective, with the exception of GEM plus Erlotinib, which showed a slight increase in OS to 6.4 months. However, some trials – mainly those using platinum based combinations – have shown an increase in response rate and time to progression.

The combination of GEM and oxaliplatin (GEMOX regimen) has been reported by Louvet et al, to be active in first-line therapy against advanced and metastatic pancreatic cancer. GEMOX has also been shown to provide significantly better RR, clinical benefit response (CBR) and period-free survival (PFS) than GEM alone. Furthermore, toxicity with this combination is limited.

The GEMOX combination was shown to have a survival benefit of an additional 2 months, but this difference was not significant. Possible causes of this could be the lack of power in the statistical assumption, the inclusion of a high number of locally advanced diseases (LAD), and the proportion of second-line therapy using a platinum-based regimen. A recent metanalusis suggested that GemOx prolongs survival, which none of the individual trials showed.

However, there are still no guidelines or recommendations for selecting treatment for patients progressing after GEM therapy; nor are there any reports of regimens with demonstrated activity that would enable one to justify one approach over another. 2010 NCCN does not list gemcitabine oxaliplatin although it lists gemcitabine cisplatin.
There is on ongoing study that is no longer recruting: Gemcitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced or Metastatic Unresectable Pancreatic Adenocarcinoma, NCT00075452. NCCN lists a study of CapOx, versus GemOx and GemCapOx and mentions interim findings on p. 41 but also taht the study is ongoing.

A Demols et al,Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study, British Journal of Cancer (2006) 94, 481-485.

Louvet C, André T, Lledo G, Hammel P, Bleiberg H, Bouleuc C, Gamelin E, Flesch M, Cvitkovic E, de Gramont A (2002) Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 20(6): 1512–1518

Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, Zaniboni A, Ducreux M, Aitini E, Taieb J, Faroux R, Lepere C, de Gramont A (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23(15): 3509

H. Q. Xiong, R. A. Wolff, K. R. Hess, G. R. Varadhachary, J. C. Blaisand J. L. Abbruzzese A phase II trial of oxaliplatin plus capecitabine (xelox) as second line therapy for patients with advanced pancreatic cancer Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 4119

FOLFOX-6 Combination in the First-Line Treatment of Locally Advanced and/or Metastatic Pancreatic Cancer. ASCO 2006, Abstract 106]

Cholangiocarcinoma is a cancer of the bile ducts, which drain bile from the liver into the small intestine. It is a relatively rare cancer, with an annual incidence. If the tumor cannot be surgically removed, patients are often treated with palliative chemotherapy with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable cholangiocarcinoma. There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin, irinotecan, or capecitabine. Combined chemoradiation, although often done, is not proven and NCCN recommends it on a clinical trial. PDQ says, “For patients with locally unresectable tumors, preoperative radiation therapy with various chemotherapeutic agents and/or radiosensitizers is under clinical evaluation.” A recent guideline in Gut, referenced below states : “The role of chemoradiation (chemotherapy combined with local radiation) remains to be established in randomised clinical trials as local and systemic toxicity is also concomitantly increased.” As per paln language, it is evident that theh consensus of experts is that clinical nvestigtion is required for this approach. It is , therefore, investigational. NCCN, however, lists chemoradiation as a standard recommendation and it is a later guideline.

http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf

http://www.cancer.gov/cancertopics/pdq/treatment/pancreatic/HealthProfessional/page7/print

S A Khan et al Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document Gut 2002;51

Aan older regimen of IV 5FU, leukovorin, mitomycin, streprozocin has been well studied in pancreatic cancer. One prospective randomized trial published in 2006 compared streptozotocin, mitomycin C, and 5-FU (SMF) with mitomycin C and 5-FU (MF) in patients with advanced pancreatic cancer. In patients with measurable disease the response rates were 34% (19/56) to SMF, and 8% (5/60) to MF (P = 0.009). Median survivals were similar, however, 18 versus 17 weeks (P = 0.356). Median survival of patients responding to chemotherapy was 33 weeks, and for nonresponders it was 17 weeks (P = 0.002). In patients with nonmeasurable disease, median survivals were 21 weeks (SMF) and 18 weeks (MF) (P = 0.797). Patients surviving 48 weeks, however, appeared to be increased in the SMF arm (14 patients) compared to the MF (7 patients). Toxicity was moderate for both regimens, with SMF having greater gastrointestinal and renal toxicity. Chemotherapy with SMF appears to produce objective responses in patients with pancreatic cancer, but does not improve survival compared to MF.

The regimen had been compared to others in older trials. Generally it was found to be comparable to other combination chemo regimens in terms of response but not superior in survival.

NCCN provides  several choices, among them gemcitabine and capecitabine,  Adjuvant gemcitabine plus capecitabine significantly improved overall survival compared with gemcitabine monotherapy in patients with pancreatic ductal adenocarcinoma, according to results of the ESPAC-4 trial presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.

Regine, W. F., Winter, K. A., Abrams, R. A., Safran, H., Hoffman, J. P., Konski, A., Benson, A. B., Macdonald, J. S., Kudrimoti, M. R., Fromm, M. L., Haddock, M. G., Schaefer, P., Willett, C. G., Rich, T. A. (2008). Fluorouracil vs Gemcitabine Chemotherapy Before and After Fluorouracil-Based Chemoradiation Following Resection of Pancreatic Adenocarcinoma: A Randomized Controlled Trial. JAMA 299: 1019-1026

Benson, A. B. III (2007). Adjuvant Therapy for Pancreatic Cancer: One Small Step Forward. JAMA 297: 311-313

Neoptolemos JP, Palmer D, Ghaneh P, et al. ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma. Oral presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.

nccn, Pancreatic 2017, PANC-5 and PANC-J