The current role of chemotherapy in pancreatic carcinoma is limited, and progress in the treatment of this disease represents a significant challenge to medical oncology. The most promising drug under study is gemcitabine, a relatively new antimetabolite that represents an attractive candidate for combination chemotherapy because of its excellent side-effect profile and the absence of overlapping toxicities with other chemotherapeutic agents. Combined administration of gemcitabine and anthracyclines could result in the induction of DNA breaks that are not easily repaired by the cell's machinery, thus enhancing the apoptotic signals triggered by these lesions. Forty-four patients with locally advanced and/or metastatic pancreatic adenocarcinoma were enrolled in this multicenter study. Patients received Epirubicin 20 mg m 72 for 3 weeks followed by 1 week of rest (1 cycle) and gemcitabine 1000 mg m 72 after Epirubicin on the same day. All were assessable for toxicity and response, 11 patients responded to treatment with one complete response and 10 partial responses, for an overall response rate of 25%. Median survival was 10.9 months (range, 2 -26 months). Therapy was well tolerated, with a low incidence of haematologic grade 42 toxicity. A total of 12 of 27 (44.4%) eligible patients attained a clinical benefit response. Our findings suggest that the gemcitabine-epirubicin schedule is active and well tolerated in patients with advanced pancreatic cancer.

We report the case of a patient affected by an extra-nodal non-Hodgkin lymphoma presenting as a unique, large retroperitoneal mass with an unusual clinical presentation mimicking gastric peptic or neoplastic disease. The patient was successfully treated with a first generation therapy, CHOP modified regimen (cyclophosphamide 600 mg/m2 intravenously on d 1, epirubicin 55 mg/m2 intravenously on d 1, vincristine 1.2 mg/m2 intravenously on d 1, prednisone 60 mg/m2 on d 1-5), and a complete response was achieved. The (18)F-fluorodeoxyglucose positron emission tomography was used to assess the therapy outcome. A brief review of literature is provided.

For advanced colorectal carcinoma, two new drugs, raltitrexed (TOM) and oxaliplatin (L-OHP), have recently shown interesting results. Preclinical and clinical studies suggest that this combination, because of its favorable toxicity profile, high response rate and convenient schedule of administration, can be administered successfully in this disease. In our phase II study, 37 non pre-treated patients with metastatic colorectal carcinoma were treated with TOM (3 mg/m(2)) and L-OHP (130 mg/m(2)) every 3 weeks. In total, 222 cycles were administered; all patients received at least 2 cycles (median 6, range 2-8). There were two complete and 14 partial responses for an overall response rate of 43% (95% CI 27-69%). The median time to response was 2.5 months (range 2-4) and the median duration was 10.3 months (range 5-18). Twelve of the 23 (52%) patients with symptomatic colorectal cancer were classified as clinical benefit responders for at least 4 weeks during the study period. Treatment was well tolerated, and both acute, essentially hematologic, and cumulative hepatic and neurologic toxicities were manageable and reversible. Response rate and toxic effects observed during this study warrant additional studies comparing this TOM-L-OHP regimen with CPT-11 and/or capacitebine-containing regimens in metastatic colorectal carcinoma.

The efficacy of weekly paclitaxel in androgen-independent prostate cancer and its addictive cytotoxicity with anthracycline derivatives led us to determine the safety and efficacy of a weekly schedule of paclitaxel and epirubicin. Between October 2000 and November 2002, 32 patients were enrolled in this study. Patients characteristics included a median age of 72 years (range 68-77), adequate hepatic, cardiac, renal and bone marrow functions, ECOG performance status of 1-2, and no prior chemotherapy. All patients had received hormonal manipulation and seven patients (22%) had received prior palliative radiation therapy. The regimen consisted of paclitaxel 70 mg/m2 i.v. infusion for 2 h and epirubicin 30 mg/m2 in bolus every week. Treatment was continued for 3 months or until disease progression or unacceptable toxicity were observed. During the study, prostate-specific antigen (PSA) was monitored and response was defined as a 50% reduction in PSA levels, to be confirmed 4 weeks later. Thirty-one patients were evaluable for toxicity and 21 for objective response. Seventeen patients (57%) had a decline above 50% in PSA level that lasted more than 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 5.5 months. Ten of the 21 patients with measurable disease (47%) had a confirmed objective response (one complete response and 20 partial responses). Thirteen of 25 symptomatic patients (56 %) had improvement in pain. The median time to disease progression was 7.6 months and the median survival was 12.9. The most prominent grade 3 toxicities were reversible myelosuppression and fatigue. Nausea, vomiting, diarrhea and peripheral edema were minimal. No evidence of cardiac toxicity was recorded. Alopecia was frequent, but reversible, in all patients. We conclude that despite the small sample size, this study demonstrates that the combination of weekly paclitaxel and epirubicin is a well-tolerated regimen for androgen-independent prostate cancer. The results imply that a combination of these agents in a weekly schedule may have clinical potential in prostate cancer treatment.

The overall survival for patients with metastatic melanoma is very poor, with a median survival of 8.5 months. In this Phase II trial, we assessed the efficacy, safety, and tolerability of a sequential biochemotherapy schedule, using dacarbazine as antiblastic agent and immunomodulant doses of interleukin-2 and interferon-alfa. Thirty-one eligible patients with metastatic melanoma received dacarbazine IV as antiblastic therapy and interluekin-2, plus interferon-alfa SC as sequential immunotherapy, for 6 months. Responding and nonprogressing patients were subsequently maintained on immunotherapy treatment for further 6 months. Twenty-nine patients had an adequate trial, and were assessable for both response and toxicities, with a median follow-up of 49 months. The overall response rate was 52 percent (3 CR and 12 PR), SD was 8 (27 percent) and PD were achieved in 6 patients (21 percent). The median survival duration of responders was 28 months, significantly longer (p < 0.001) than the 16 months of nonresponders. Therapy was well tolerated and produced a significant improvement in progressive-free survival. Further studies, thus, are recommended for larger groups of patients not only to confirm these results, but also to apply this biochemotherapy regimen as adjuvant postsurgical treatment in early stages of malignant melanoma.