Vitamin D status and per-oral vitamin D supplementation in patients suffering from chronic pancreatitis and pancreatic cancer disease.

UNLABELLED: Exocrine pancreatic insufficiency due to chronic pancreatitis may result--depending on the degree of insufficiency--, in a decrease in serum 25-hydroxyvitamin D (25(OH)D) level. However, the data in the literature concerning the rate and extent of vitamin D deficiency in pancreatic cancer with or without previous pancreas resection, are very rare, in particular regarding the question how to supplement these patients with vitamin D. In recent years, vitamin D is increasingly being discussed as one factor involved not only in musculo-skeletal diseases but also in cardiovascular and autoimmune diseases, cancer development, diabetes mellitus and overall mortality. PATIENTS AND METHODS: In all, 248 ambulatory patients (n=140 patients suffering from exocrine pancreatic insufficiency due to chronic pancreatitis, pancreatic cancer with/without previous resections of the pancreas n=108 patients without pancreatic disease), we measured the serum 25(OH)D concentrations by the chemoluminescence method. In addition, in 91 of these patients (n=65 pancreatic patients, n=26 controls), we started supplementation with oral vitamin D in combination with dietary advice and adequate substitution with pancreatic enzyme preparations, followed by subsequent serum 25(OH)D determinations. The oral vitamin D doses varied from 1000 IU per day over 1× 20,000 IU per week, or 2-3 times 20,000 IU per week up to 20,000 IU per day in single patients, depending on the underlying disease and the estimated degree of maldigestion/malassimilation. In addition, in a pilot trial vitamins A and E were measured in the serum from 121 and 105 of these patients respectively (resp.) (HPLC method). RESULTS: Serum 25(OH)D concentrations were <30 ng/ml in 93% of the patients with pancreatic diseases,<20 ng/ml in 77.9%, <10 ng/ml in 32.1% and <4 ng/ml in 9.3%. The results were comparable to those in patients suffering from chronic pancreatitis and those with pancreatic tumor disease, with or without a previous tumor resection (n=51 Whipple procedure, n=11 left resection, n=9 total duodeno-pancreatectomy). Similar data were also found in the controls, only slightly higher. In contrast to the vitamin D data, however, determination of vitamins A and E in the serum resulted in values within the normal range for the majority of the patients of both groups, suggesting a diminished vitamin D uptake as being at least one reason to explain the low serum vitamin D concentrations in the patients with pancreatic diseases. Individual supplementation with oral vitamin D in all patients studied (n=91) resulted in an increase of the serum 25(OH)D concentrations into the normal range (14.2±5.8 up to 42.3±12 in controls, 11.9±7.4 up to 46.6±15.7 in patients with pancreatic diseases). The data of a subgroup of patients with continuous long-term supplementation, however, suggest that some patients with pancreatic diseases may need a significantly higher vitamin D supplementation, up to 20000 IU per day in single patients, compared to the controls. CONCLUSION: The results demonstrate that vitamin D deficiency is a common problem in patients suffering from exocrine pancreatic insufficiency from various reasons as well as in our controls. Apart from insufficient sun exposure, exocrine pancreatic insufficiency, as well as a too low vitamin D uptake with food seem to represent the main causes of low serum 25(OH)D. In nearly all patients, the serum 25(OH)D concentrations could be normalized by oral supplementation of vitamin D in the case of individual therapy based on routine serum controls.

Combination therapy with gemcitabine (GEM) and erlotinib (E) in exocrine pancreatic cancer under special reference to RASH and the tumour marker CA19-9.

We report on the results of a prospective treatment of 30 proven metastatic pancreatic cancer patients with the recently described combination of gemcitabine and erlotinib (GEM+E) (24× 1st line therapy, 8× 2nd line therapy). Eight of these patients received GEM+E for treatment of metastastic tumour recurrence after previous resective surgery, followed by adjuvant chemotherapy with gemcitabine. In 2 patients GEM+E was given as 1st line treatment and later, after complete response which was followed by a new recurrence, also as a second line therapy. The evaluation of RASH severity grades, the course of the serum tumour marker CA19-9 were determined every 14 days and the evaluation of the imaging methods CT or MRT, evaluated every 6-8 weeks, revealed the following results: there was a tendency for RASH grades to correlate with the tumour response, however, with observed exceptions. The decision for interruption or maintenance of GEM+E, therefore, should not be based on the RASH phenomenon, but on a detailed follow-up with imaging methods and the relevant tumour markers as in the follow-up before erlotinib introduction into pancreatic cancer therapy. As known from previous studies tumour markers represent more sensitive parameters compared to the imaging methods. GEM+E was active in the whole group of patients, mainly given as 1st line therapy (34% PD, 29% SD, 47% MR, PR, CR), but also in the 2 subgroups: in the patients with GEM+E as 2nd line therapy, as well as in patients after previous adjuvant gemcitabine therapy after tumour resection. In the 2 patients with transient-CR after 1st line therapy with GEM+E the 2nd line therapy also resulted in a CR with long lasting remission. These data should motivate clinicians to focus their interest not only to 1st line therapy regimens with erlotinib, but also to 2nd and 3rd line strategies within the previously published concept of an efficacy-orientated sequential polychemotherapy or multimodal-therapy for pancreatic cancer.

CA19-9 serum concentrations--analysis of the serum kinetics during first-line therapy of pancreatic cancer in relation to overall survival.

In order to investigate the use of CA19-9 serum concentration kinetics during first-line chemotherapy of pancreatic cancer as a potential predictive prognostic factor for overall survival, we retrospectively analysed the data of 47 patients suffering from proven exocrine pancreatic cancer. The patients were treated following our concept of efficacy-orientated sequential palliative chemotherapy (EOSPC), on the basis of a short-term follow-up including CA19-9 determinations at least monthly and imaging methods CT and/or MR every 2 months. The results are in agreement with our previous reports suggesting an increase of survival of pancreatic cancer patients in relation to the number of effective treatment regimens applied. However, apart from a weak correlation between the lowest CA19-9 levels induced by the first-line therapy (as a % of the initial pretherapeutical CA19-9 levels) and progression-free survival there was no correlation between the various parameters of serum kinetics of CA19-9 in the course of the first-line therapy and overall survival of the patients. A potential correlation as reported by others seems to be confirmed in our patient group by the potential antitumoral and life-prolonging effects of the second- and third-line therapies.