Clinical and molecular determinants of survival in pancreatic cancer patients treated with second-line chemotherapy: results of an Italian/Swiss multicenter survey.

BACKGROUND: Increased knowledge about the treatment of pancreatic cancer has influenced the management of locally advanced and metastatic disease. Nonetheless, prognosis remains dismal (24%, 1-year survival). The impact on overall survival (OS) of second-line therapy has not been clarified and the use of platinum salts and/or fluoropyrimidines is hotly debated. It is the hope that future treatment can be tailored to predict chemosensitivity in order to improve outcomes in patients with locally advanced and metastatic pancreatic cancer. Since DNA-damaging agents could be one therapeutic option, a retrospective multicenter study was performed to evaluate the efficacy of salvage treatment with the hypothesis that levels of the DNA repair gene excision repair cross complementing 1 (ERCC1) could influence OS. PATIENTS AND METHODS: In a population of 160 patients treated with fluoropyrimidine-based second-line chemotherapy, expression levels of ERCC1 were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). In 108 patients with locally advanced and metastatic pancreatic cancer treated with either fluoropyrimidines and platinum salts (group A=58) or fluoropyrimidines alone (group B=50), ERCC1 levels were correlated with OS, time to progression and response to chemotherapy. RESULTS: Median survival was significantly higher in group A with low ERCC1 levels [11.9 versus 9.9 months; p ≤ 0.05] (median follow-up 24 months). Moreover in the same group, a trend towards longer time to progression was observed. No differences in OS were observed when ERCC1 was studied (low versus high) in patients not treated with platinum salts. On multivariate analysis of pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for OS. CONCLUSION: The results of this study indicate that ERCC1 may predict survival in pancreatic cancer patients treated by platinum and fluoropyrimidine as second-line chemotherapy.

ChlVPP/ABVVP, a first line 'hybrid' combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysis.

We retrospectively analysed toxicities and clinical results of 61 Hodgkin's lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III-IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6-8 cycles. Involved field radiotherapy (IFRT) (30-35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow-up of 60 months, 5-year overall survival, relapse- and event-free survival were 78.8% (95% CI 68.2-91.1%), 81% (95% CI 70.6-92.2%) and 71.9% (95% CI 68.2-82.2%) respectively. Grades 3-4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non-haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non-haematological toxicity. Long-term results of the ongoing randomized trial, comparing ABVD versus high-dose intensity weekly regimens will be useful to confirm our results.

Efficacy of vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy with involved field radiotherapy in early stage (I-IIA) Hodgkin disease patients.

Vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy (CT) with involved field radiotherapy (IFRT) was first described by the Stanford group as an active regimen in early stage Hodgkin's disease (HD). Here, we report our retrospective experience of a modified VBM schedule + IFRT in a similar group of patients. From 1988, 49 patients with stage I-IIA HD received vinblastine (VBL) 6 mg/m2, bleomycin (BLM) 10 IU/m2, methotrexate (MTX) 30 mg/m2 day 1,8 every four weeks for three cycles; IFRT was delivered four weeks later followed by three additional cycles of VBM with a dose reduction of BLM (6 IU/m2). The regimen was well tolerated, with grade 3-4 neutropenia occurring in 20 patients. No acute or late pulmonary toxicity was recorded in our series. Estimated Freedom from Progression (FFP) and Overall Survival (OS) at five years are 75% (95% CI, 60.1%-92.2%) and 85% (95% CI, 73.6%-98.1%), respectively. In this retrospective analysis, VBM + IFRT treatment with bleomycin dose reduction seems safe and active. Such combination could be considered as first line treatment for early stage HD patients with favorable prognosis and/or not suitable for anthracyclines-containing regimens.