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Background: Irinotecan and raltitrexed are active agents in advanced colorectal cancer (ACC) and preclinical data suggest a remarkable synergistic activity. Phase I studies demonstrated that single-agent full dose of both drugs can be administered with moderate toxicity. The aim of this phase II trial was to assess the activity and tolerability of the combination in untreated ACC., Patients and Methods: Forty-eight patients entered the trial and received irinotecan 350 mg/m2 d.1 and raltitrexed 3 mg/m2 d.2, every three weeks. After recruitment of the first 16 patients, grade III-IV toxicity was observed in 6 patients (38%). Therefore, an amendment reduced by 15% the dose of both drugs (irinotecan 300 mg/m2, raltitrexed 2.6 mg/m2)., Results: A total of 290 cycles were administered (range 1-18, median number 6). According to intention-to-treat analysis, the overall response rate was 27% (95% confidence interval 16%-42%), including 3 complete responses and 10 partial responses. The median duration of response was 10 months, while median progression-free survival and overall survival were 5 and 14 months, respectively. In the first 16 patients, the main toxicities were grade III-IV diarrhea in 25% and grade III-IV neutropenia in 13%. In the subsequent 32 patients, they were grade III-IV diarrhea in 34% and grade III neutropenia in 6%. Two toxic deaths occurred., Conclusion: The combination irinotecan-raltitrexed is an active regimen, but the significant incidence of side-effects requires accurate patient selection and, eventually, new schedules.

Background: Chemotherapy with oxaliplatin, fluorouracil (5-FU) and leucovorin (LV) has proven efficacy in patients with advanced colorectal carcinoma (CRC), although the optimal dosage and administration schedule are still unclear. This phase II trial investigated the tolerability and activity of weekly oxaliplatin, high-dose infusional 5-FU and LV in pretreated patients with metastatic CRC., Materials and Methods: Patients received weekly courses of i.v. oxaliplatin 50 mg/m2 (1-h infusion), LV 100 mg/m2 (1-h infusion) and 5-FU 2100 mg/m2 (24-h infusion) until disease progression or unacceptable toxicity. NCI-CTC criteria were used for assessment of side-effects (at each cycle) and WHO criteria for assessment of tumour response (every 8 cycles). For descriptive purposes, time to progression, overall survival and duration of objective response were also calculated., Results: Forty-four patients were enrolled and received a total of 606 cycles (median 13/patient, range 4-33), and 70% of courses (421/606) were delivered at 100% of the planned dose. The most frequent side-effects were gastrointestinal and neurological and incidence rates were: diarrhoea 66% (grade III: 29%), nausea/vomiting 54%, neurotoxicity 34% (grade III: 2%), fatigue 27%, mucositis 22%, leucopenia 14%. No grade IV toxicity was observed. Objective response rates were: partial response 23% (10 patients), stable disease 59% (26) and progressive disease 11% (5). Median time to progression was 7 months, overall survival 13 months and the duration of partial response and stable disease were 9 and 6 months, respectively., Conclusion: The study demonstrated that this regimen has a favourable tolerability profile and is an active combination in the pretreated metastatic CRC patient, deserving further evaluation in phase III trials.

The role of elective lymph node dissection (ELND) for the treatment of cutaneous melanoma has been debated for many years. Actually, the value of ELND is seriously questioned because an increasing of overall survival rates has not been demonstrated. The lymphatic mapping technique, initially performed by an intradermic injection of vital blue dye, subsequently improved by the use of radioguided surgery (RGS), proved effective for the detection of clinical occult lymph node metastasis. We performed a sentinel node biopsy on 71 patients with stage pT2/T3N0M0 melanoma. Vital blue dye mapping alone was performed on 39 patients; the remaining 32 patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel node (SN) was complexively identified in 69/71 (97.2%) patients. Sixteen patients (23.2%) were found to have metastatic melanoma cells in their SN(s); all these patients underwent lymph node dissection of the affected basin. Our experience confirmed that the intraoperative detection of sentinel nodes using both blue dye and radio-guided surgery is an effective and reliable technique for selecting patients to be submitted to lymph node dissection.

Background: Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken., Patients and Methods: Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines., Results: The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively., Conclusions: L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.

Pseudomixoma peritonei is a rare neoplasm characterized by mucinous ascites and the mucinous involvement of peritoneal surfaces, omentum and bowel loops. Usually pseudomixoma peritonei is associated with benign or malignant mucinous tumor of the appendix or ovary. The diagnosis of pseudomixoma peritonei is difficult because laboratory and radiology results are frequently nondiagnostic. We report a case that was initially mistaken for carcinomatosis of unknown origin and that underwent cytoreductive procedure and omentectomy as the treatment of choice.

Primary and metastatic gastrointestinal tumours in the liver have been treated by intrahepatic artery infusion of chemotherapeutic drugs in an attempt to increase the efficacy of the administered agents. Among the several active agents, 4' epidoxorubicin, an anthracycline analogue, was selected for this study because of the therapeutic level reached in the liver by this drug. Seven patients with primary hepatic carcinoma and twenty with metastatic adenocarcinoma of the colon to the liver received intraarterial hepatic infusion of epidoxorubicin at the dosage of 30 mg weekly. No haematological or gastrointestinal grade 3-4 toxicity was recorded, only one patient experienced transient cardiac toxicity. No objective response was observed in primary hepatic carcinoma and six objective responses, 1 complete and 5 partial (30%), were achieved in metastatic colorectal cancer patients. This results is not far from those reported with FUDR, but does not justify epidoxorubicin in colorectal cancer patients as first line intraarterial treatment.