Alessia Rognone

Carbohydrate Antigen 19-9 Change During Chemotherapy for Advanced Pancreatic Adenocarcinoma

Radiologic assessment of tumor response in pancreatic cancer is complicated by desmoplastic reactions within or around the tumor. The objective of this study was to evaluate the correlation between a decline in carbohydrate antigen 19‐9 (CA 19‐9) and survival in patients with advanced pancreatic cancer who received upfront chemotherapy.

Colorectal carcinoma in children and adolescents: the experience of the Istituto Nazionale Tumori of Milan, Italy.

Colorectal carcinoma (CRC) is one of the most common tumors in adults, but extremely rare in young age. This study retrospectively reports on a group of 27 patients <30 years of age, and particularly on 7 cases <18 years old, treated at the Istituto Nazionale Tumori, Milan, Italy, between 1985 and 2005.

Salvage therapy with mitomycin and ifosfamide in patients with gemcitabine-resistant metastatic pancreatic cancer: A phase II trial

Background: At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. Methods: Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m2 on day 1, ifosfamide 2,500 mg/m2 and mesna 3,000 mg/m2 on days 1–3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrolment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. Results: Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. Conclusion: Based on the poor outcome observed and on the high level of grade 3–4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.

Second-line therapy in advanced biliary tract cancer: What should be the standard?

Biliary tract cancer is a rare malignant tumor. Accordingly, to perform prospective and randomized trials is difficult and the knowledge of its natural history and optimal management remains limited. Chemotherapy is commonly used to improve the outcome and to delay tumor progression in advanced disease. Only recently, cisplatin-gemcitabine combination was identified as the new standard first-line therapy. Despite the outcome improvement, disease progression is a constant and approximately half of patients failing upfront treatment maintain a good performance status and are willing to undergo further treatment. No standard salvage chemotherapy regimen has been identified yet. Experiences of salvage therapy in advanced biliary tract cancer are sparse and yielded disappointing results. Well designed multi-institutional randomized trials are warranted to clarify the role and the activity of a second-line therapy.

An Italian study on treatment trends and outcomes of patients with stage III pancreatic adenocarcinoma in the gemcitabine era: is it time to change?

A series of 650 patients treated between 1997 and 2007 at 10 Italian centers was analyzed to assess treatment trends and efficacy in stage III pancreatic adenocarcinoma. Data on patient characteristics, treatment and outcomes were collected. The inclusion criteria were pathological diagnosis of stage III pancreatic adenocarcinoma; age more than 18 years, Eastern Cooperative Oncology Group performance status less than 3, and no past therapy. Most patients (95%) received upfront chemotherapy, which mainly consisted of gemcitabine alone (N=323), gemcitabine-based four-drug combinations (N=107), gemcitabine-platinum compound doublets (N=87), or intra-arterial gemcitabine-free triplets (N=57). The use of gemcitabine–platinum compound doublets increased over time (1997–2001: 2%; 2002–2007: 21%) whereas an inverse trend was observed for gemcitabine (71–61%). No overall survival (OS) difference was observed between patients enrolled in clinical trials and those not enrolled. The median and 1-year OS were 9.5 months and 35.5% for patients treated with gemcitabine; 8.9 months and 36.8% for those treated with gemcitabine-free intra-arterial triplets; 13.3 months and 55.8% for those treated with gemcitabine-platinating agent doublets; and 16.2 months and 62.6% for those treated with gemcitabine-based four-drug combinations. Moreover, the median and 1-year OS were 12.7 months and 51.4% in patients who underwent planned consolidation chemoradiation, and 8.4 months and 30.4% in patients who did not. The use of a strategy consisting of a gemcitabine-platinating agent containing chemotherapy followed by consolidation chemoradiation has been increasing over time and may represent a suitable choice in the therapeutic management of stage III pancreatic adenocarcinoma.

Treatment trends in metastatic pancreatic cancer patients: Is it time to change?

BACKGROUND Since gemcitabine became the standard treatment for metastatic pancreatic adenocarcinoma, combination chemotherapy obtained conflicting impact on survival (OS). AIMS To evaluate Italian treatment trends in metastatic pancreatic cancer. METHODS Data on treatment outcome of 943 chemo-naive patients with pathological diagnosis of stage IV pancreatic adenocarcinoma treated between 1997 and 2007 in Italian centres were analysed. RESULTS Four treatment groups could be identified: (1) single agent gemcitabine (N=529); (2) gemcitabine-platinating agent doublets (N=105); (3) gemcitabine-free three-drug intraarterial combination (N=75); (4) four-drug gemcitabine-cisplatin-fluoropyrimidine based combinations (N=170). Median and actuarial 1 y OS of the whole population were 6.2 months and 20%, respectively. Gemcitabine (median OS 5.1 months) appeared significantly inferior to gemcitabine-free triplets (median OS 6.0 months; p=.04), gemcitabine-platinating agent doublets (median OS 7.4 months; p=.00001), or gemcitabine-based four drug combinations (median OS 9.1 months; p<.00001). CONCLUSION These data mirror the Italian clinical practice in the therapeutic management of pancreatic cancer and suggest that four-drug combination chemotherapy may be included amongst the candidate regimens for phase III testing.

Weekly epirubicin as salvage therapy in patients with gemcitabine-resistant advanced pancreatic cancer

Pancreatic cancer is one of the most aggressive human cancers with extremely poor prognosis. Gemcitabine has improved clinical benefit in comparison to bolus 5-fluorouracil in a phase iii study 1 and is currently regarded as the standard treatment for advanced pancreatic cancer yielding an objective response rate in 4-26% of patients and a 1-year overall survival (Os) of 17-28% 1-2. Due to the marginal impact on disease outcome, several attempts to improve the efficacy of gemcitabine by adding one or more drugs have been made. Unfortunately, no clinically relevant Os improvement occurred. Tumor progression usually occurs within a few months after the start of first-line treatment. in fact, median progression-free survival with single agent gemcitabine is approximately 3 months and less than 15% of patients remain free of progression at 6 months (PFs-6) from diagnosis 1-2. in spite of progressive disease, over half of patients maintain a good performance status and are willing to undergo further treatment. Recently, results of a randomized phase ii trial suggested that salvage therapy might offer some benefit when compared to best supportive care 3. Epirubicin is a doxorubicin analogue whose activity against pancreatic cancer is reported both in the preclinical 4 and clinical setting in chemo-naïve patients 5,6. since the therapeutic armamentarium against pancreatic cancer is limited, we decided to explore the activity of this drug, which was previously licensed in italy for pancreatic cancer treatment, as salvage therapy in patients with gemcitabine-resistant disease. Patients aged 18 to 76 years, with cytologically or histologically proven advanced pancreatic adenocarcinoma, adequate bone marrow (absolute neutrophil count (AnC) ≥1500 cells/mm3; platelet count 100000 cells/mm3 and hemoglobin ≥10 g/dl); kidney (serum creatinine ≤1.5 mg/dL) and liver function (serum total bilirubin ≤1.5 mg/dL and serum transaminases ≤5 upper limit of laboratory normal) and progressive disease after gemcitabine-based chemotherapy, underwent salvage treatment with weekly epirubicin at 35 mg/m2 day 1, 8, 15 every 28 days until progression, unacceptable toxicity, the patient’s refusal or medical decision. Patients with at least one measurable indicator lesion according to RECisT criteria were considered assessable for response evaluation 7. Assessment of disease, including CA19.9 measurement and high-resolution CT scan of the abdomen and chest, was done at baseline, every 6-8 weeks during chemotherapy and then every 2 months or when disease progression (PD) was clinically suspected. Complete blood, platelet and differential counts were done every week, while biochemistry profile was done on a monthly basis. Toxicity was graded according to the nCi-CTC version 3.0 8. PFs was calculated as the interval between the initiation of treatment and the occurrence of PD or death. survival was measured from initiation of treatment to date of death or to the last follow-up assessment. This was an observational trial and was approved by an internal review board. All participating patients were required to give written informed consent. As this was an observational study, no statistical design was performed. survival curves were calculated using the Kaplan-Meier method and univariate analyses, and compared by means with the log-rank test. All probability values were from two-sided tests. Analyses were performed using statistica 4.0 for Microsoft Windows. Between February 2007 and April 2008, 15 patients with progressive pancreatic adenocarcinoma after gemcitabine-based chemotherapy were treated at our institution. Patients’ characteristics at baseline are summarized in table 1. Previous median PFs, which was calculated as the interval between the start of the previous chemotherapy (table 1) and radiological demonstration of PD or recurrence preceding epirubicin administration, was 3.3 months for all patients (range 1.1-7.8 months) and only 2 patients had a previous PFs >6 months. sixty-four weekly doses of epirubicin were administered. The median duration of chemotherapy was 5 weeks (range 1-7 weeks). Dose intensity was 94% of the intended weekly dose. Therapy was discontinued prior to completion in all patients due to radiological PD (n=5) or clinical deterioration (n=10). Treatment-related toxicity was mild and only 3 patients presented grade 3-4 toxicity. One patient experienced grade 4 neutropenia, 3 grade 3-4 anemia and REpRInt

Metastatic Site in Pancreatic Adenocarcinoma Correlates with Prognosis

Context Pancreatic adenocarcinoma (PA) is mostly metastatic at time of diagnosis with a poor survival. Objective We decided to explore whether metastatic site correlates with prognosis. Methods Patients with pathologic diagnosis of metastatic PA, treated at our Institution with upfront combination chemotherapy between April 1997 and August 2010 were eligible for this analysis. Baseline tumor assessment consisted of contrast enhanced computed tomography scan of the abdomen and the thorax. Results Two-hundreds and sixty-five patients with metastatic PA, median age 60 years; median PS 90; median CA 19-9 1,048 were eligible; 19 (7.2%) had prior pancreatic surgery. Metastases were located: in a single organ (n=150; 56.6%); liver (n=227; 85.3%); peritoneum (n=32; 12.1%); lung (n=53; 19.9%). Lung was the only metastatic site in 15 cases (5.6%). Median and 1-year overall survival (OS) was 9.0 months and 32.2%. Prior surgery correlated with better OS (11.7 and 51.0% versus 8.9 and 30.8%; P=0.006); liver metastases with worse OS (median and 1-year OS: 8.8 months and 29.7% versus 11.1 and 47.4%; P=0.005); while no difference in OS was observed based on number of metastatic sites (P=0.37); peritoneal (P=0.50) or lung metastases (P=0.10). Patients with lung as isolated metastatic site lived longer (17.3 months and 66.7%) with respect to the whole population (9.0 months and 30.1%; P=0.01) and to patients with lung metastases associated to other metastatic sites (8.8 months and 34.2%; P=0.07). Conclusions Prior surgery and metastatic site correlate with prognosis and should be used as a stratification criterion in prospective trials. Patients with lung as isolated metastatic site has a particularly good prognosis.