Massimo Lopez

Phase III Randomized Trial of FOLFIRI Versus FOLFOX4 in the Treatment of Advanced Colorectal Cancer: A Multicenter Study of the Gruppo Oncologico Dell’Italia Meridionale

PURPOSEnWe performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer.nnnPATIENTS AND METHODSnA total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2 regimen).nnnRESULTSnOne hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed.nnnCONCLUSIONnThere is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: A prospective, randomized Phase III study of the gruppo oncologico dell'italia meridionale

A prospective, randomized Phase III trial was performed to determine whether, compared with gemcitabine (GEM) alone, the addition of cisplatin (CDDP) to GEM was able to improve the time to disease progression and the clinical benefit rate in patients with advanced pancreatic adenocarcinoma. The objective response rate, overall survival rate, and toxicity patterns of patients in the two treatment arms were evaluated as secondary end points.

Hormonal Treatment of Disseminated Male Breast Cancer

14 males with disseminated cancer of breast received a total of 35 endocrine trials, mainly in the form of hormonal supplementation. Overall, a 43% response rate was observed. In particular, remissions occurred in 7 of 11 instances with cyproterone acetate, in 3 of 7 with tamoxifen, in 2 of 5 with estrogens, in 2 of 5 with aminoglutethimide, in none of 3 with high-dose medroxyprogesterone acetate, in none of 1 with androgens, and in 1 of 3 with castration. The response to additive hormonal therapy was 44%. Median overall response duration was 10 months, 11 months following additive hormonal therapy. Median survival from start of therapy was longer in responding than in nonresponding patients (23.5 vs. 11 months). A disease-free interval did not appear to influence hormonal response. Patients responding to one form of hormonal treatment had a greater likelihood of responding to subsequent hormonal manipulations. Additive hormonal therapy may provide effective palliation in males with advanced breast cancer, and should be considered as a valid alternative to orchiectomy.

A prospective randomized trial of doxorubicin versus idarubicin in the treatment of advanced breast cancer

Seventy‐six patients with advanced breast cancer were entered into the current study. They were randomized to receive either idarubicin (IDA) 45 mg/m2 orally or doxorubicin (DX) 75 mg/m2 intravenously (IV), both drugs being administered every 3 weeks. Among 37 evaluable patients who received DX treatment the overall response rate was 46%, whereas it was 21% in 34 evaluable patients treated with IDA. This difference was statistically significant. In previously untreated patients the response rate with DX was 60% compared to 29% with IDA. Patients with prior chemotherapy had 29% response rate to DX in contrast to 12% with IDA. The median time to response, the median response duration, and the median time to progression were similar in both groups. The median survival of all patients was 20 months in DX arm and 14 months in IDA arm (95% confidence limits 16.69–23.31 and 10.77–17.23, respectively; P = 0.09). Both treatments produced equivalent incidence and severity of myelotoxicity. Gastrointestinal toxicity and alopecia were significantly lower in patients receiving IDA. As for cardiotoxicity, four cases of congestive heart failure were recorded among patients treated with DX whereas no cases occurred in the IDA group. The results of this study indicate that, although DX remains the best single agent available in the treatment of breast cancer, IDA may have a role in selected patients with this disease. Cancer 64:2431–2436, 1989.

Combined treatment with buserelin and cyproterone acetate in metastatic male breast cancer.

Background. Male breast cancer (MBC) is considered an androgen‐dependent tumor, and as in prostatic cancer, responses have been reported with use of antian‐drogens or gonadotropin‐releasing hormone analogs. Thus, it is reasonable to postulate that better results could be achieved by combining these two agents.

5-Fluorouracil and folinic acid with or without CPT-11 in advanced colorectal cancer patients: A multicenter randomised phase II study of the Southern Italy Oncology Group

PURPOSEnThe combination regimen CPT-11 plus bolus and infusion 5-fluorouracil (5-FU) with high-dose leucovorin (hybrid regimen LV5FU2) has been tested for activity and toxicity against advanced colorectal carcinoma in a randomised, multicenter phase II trial.nnnPATIENTS AND METHODSnA total of 102 chemotherapy-naïve patients were randomised in a 1:2 fashion to receive: leucovorin 100 mg/m2 administered as a two-hour infusion before 5-FU 400 mg/m2 as an intravenous bolus, and FU 600 mg/m2 as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 (LV5FU2 regimen, arm A, 34 patients) or CPT-11 at 180 mg/m2 (150 mg/m2 for patients of age > or = 70 and < 75 years) only on day 1 immediately before LV5FU2 therapy (LV5FU2 + CPT-11 regimen, arm B 68 patients). Both treatments were repeated every two weeks. The presence of a calibration arm assured consistency and more realistic evaluation of results achieved with the LV5FU2 + CTP-II regimen.nnnRESULTSnThirty-three and sixty-four patients were evaluable in arm A and B, respectively. The overall response rate was 18% in arm A (95% CI: 7%-34%) and 40% in arm B (95% CI: 28%-52%). Median time to progression, median duration of response and survival were similar in both groups. Responders (CR + PR) survived statistically longer than non-responders only in arm B (20 vs. 10 months, P = 0.0016). All patients were evaluable for toxicity which was mild in both groups; gastrointestinal disturbances were the most common. There were no treatment-related deaths. Grade 3-4 toxicity was uncommon in both arms.nnnCONCLUSIONSnThe addition of CPT-11 to the hybrid LV5FU2 regimen provided a significant overall response rate (40%) with relatively mild toxicity. The overall response rate was 18% in patients treated with LV5FU2 alone in the calibration arm. Thus, considering other encouraging data from the literature, the CPT-11 + FU-LV combination therapy can be regarded as a new, very effective treatment option for first-line treatment of advanced colorectal cancer patients.

Chemotherapy in Metastatic Male Breast Cancer

14 male patients with metastatic breast cancer received a total of 20 chemotherapeutic trials with 2 basic combination regimens, namely, variants of the Coopers regimen CMFVP and adriamycin-containing combinations. Overall, a 35% response rate was observed. Our data suggest that cancer of the breast in the male is responsive to the same combinations used in the female, with regimens including adriamycin being probably superior to regimens without it.

5-Fluorouracil, Adriamycin, Cyclophosphamide (FAC) vs. 5-Fluorouracil, Epirubicin, Cyclophosphamide (FEC) in Metastatic Breast Cancer

94 evaluable patients with metastatic breast cancer were randomly assigned to 5-fluorouracil, adriamycin, and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), with cycles repeated every 3 weeks. The objective response rate to FAC was 46% versus 44% to FEC. There was no significant difference in the median duration of response and median survival for the two regimens. Toxicity was more frequent and more pronounced in patients receiving FAC. Results indicate therapeutic equivalence of the two regimens and reduced toxicity of the epirubicin arm.

Sequential chemoimmunotherapy for advanced non-small cell lung cancer using cisplatin, etoposide, thymosin-αl and interferon-α2a

A phase II study was performed to evaluate the clinical and immunological effects of a regimen of cisplatin (DDP) and etoposide (VP-16) combined with thymosin-alpha 1 (TA1) and low-dose interferon-alpha 2a (IFN) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemoimmunotherapy cycles were repeated every 3 weeks. There were 24 responses (two complete, 22 partial) among 56 assessable patients. Median survival was 12.6 months. Overall, treatment was well tolerated. Natural killer cell activity and lymphocyte subtypes were depressed by chemotherapy, but this effect was less prominent in patients receiving TA1 and IFN in comparison with a concomitant group of patients treated with DDP and VP-16 only. The combination of DDP and VP-16 and TA1 and IFN is effective in advanced NSCLC with acceptable toxicity. However, the results of this study need to be confirmed in a randomised trial.

Clinical relevance of radionuclide angiography and antimyosin immunoscintigraphy for risk assessment in epirubicin cardiotoxicity

BackgroundCardiotoxicity is the major limiting factor in anthracycline chemotherapy of advanced neoplastic disease. Epirubicin shows a more favorable therapeutic index than does doxorubicin, but it is still cardiotoxic. Limited data regarding epirubicin cardiotoxicity are available, and suggested guidelines for doxorubicin with left ventricular ejection fraction (LVEF) measurement may not be empirically useful for epirubicin therapy. This study evaluates the diagnostic role of antimyosin immunoscintigraphy for early identification of patients at risk for late pump dysfunction from cardiotoxicity induced by high-dose administration of epirubicin up to high cumulative dosages.Methods and ResultsChemotherapy with epirubicin was administered to 36 patients with cancer at a dosing rate of 160 mg/m2 as a bolus injection every 21 days to a cumulative dosage heart-lung ratio (HLR) measurements were performed before chemotherapy, at intermediate cumulative epirubicin dosages, at the end of treatment, and during the follow-up. LVEF decreased significantly at the end of the treatment and after therapy discontinuation. HLR values were significantly increased at intermediate epirubicin dosage levels and continued to increase to the end of the treatment but thereafter remained substantially unmodified for 3 to 6 months after therapy discontinuation. A value of HLR>1.85 at intermediate epirubicin dosage level showed a sensitivity of 95% and a specificity of 57% as a predictor of late LVEF impairment.ConclusionsLVEF appears more useful at high cumulative dosages and during follow-up to monitor late pump dysfunction, whereas HLR may be effective during the early phase of the therapy in determining which patients are at risk for development of late cardiac dysfunction.