Abstract: BACKGROUND: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated if the drug delivery rate was chronomodulated according to circadian rhythms rather than constant. The aim of the present study was to define the feasibility and efficacy of XELOX administered through a new chronomodulated schedule in untreated advanced colorectal cancer (CRC) patients. METHODS: Chemotherapy-naive patients with advanced CRC were considered eligible for the study accrual. Treatment: oxaliplatin 70 mg/m(2) continuous infusion (c.i.) for 12 h (8:00 a.m. to 8:00 p.m.) days 1, 8 plus chronomodulated oral capecitabine 1,750 mg/m(2)/die (h 8:00 a.m. 25% of total dose; h 6:00 p.m. 25% of total dose; h 11:00 p.m. 50% of total dose), days 1-14 every 21 days. RESULTS: Forty-six patients were evaluated for safety and efficacy (male/female, 20/26). Median age was 64 years (range 28-77 years). Median Eastern Cooperative Oncology Group performance status (PS) was 0 (range 0-1). A total of 324 cycles have been administered: median per patient 6 (range 3-10 courses). Median number of metastatic sites was 1. Metastatic sites distribution was as follows: liver (65.2%), lung (34.8%), and nodes (32.6%). Median follow-up was 14 months (range 6.0-40.3 months). In an intent-to-treat efficacy analysis, objective response and stable disease were recorded in 27 (58.6%) and in 16 patients (34.9%), respectively. The median response duration was 8.0 months (95% CI; 5.03-10.96 months). The median time to progression (TTP) was 9.0 months (95% CI; 6.47-11.52 months). The overall survival (OS) was not reached, with a median value > 24 months (95% CI; 23.66-36.30 months). The grade 3 toxicities were diarrhea (8.7%), liver toxicity (13.1%), fatigue (8.7%), neurotoxicity (2.2%), neutropenia (8.7%), and thrombocytopenia (2.2%). CONCLUSION: This regimen resulted of particular interest for patients with untreated metastatic CRC.
Abstract: CONTEXT: Pancreatic cancer still remains an incurable disease. The survival rate of patients in all stages of the disease is poor. Overall median survival is 3-5 months with a 12-month survival rate of 10% and a 5-year survival rate less than 5%. CASE REPORT: We report a rare case of a long-term survivor (more than 10 years) of metastatic carcinoma of the pancreas tail controlled with subsequent surgical and chemotherapeutic strategies with an acceptable performance status and quality of life. DISCUSSION: This is the fifth case reported in the literature showing that long-term survival may be achieved even in advanced pancreatic cancer.
Abstract: BACKGROUND: Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time. METHODS: Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule. RESULTS: A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%-56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 - 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 - 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 - 11.82). CONCLUSION: OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.
Abstract: BACKGROUND: Many emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines. METHODS: A phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines. RESULTS: Twenty-five patients received paclitaxel (150 mg/mq) by 3-hours infusion, followed by gemcitabine (2000 mg/mq) given as a 60 min i.v. infusion (day 1-14) for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16%) achieved a complete response, 12 (48%) a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20%) and progressive disease occurred in 4 patients (16%). CONCLUSION: The schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines.
Abstract: PURPOSE: We 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. PATIENTS AND METHODS: A 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). RESULTS: One 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. CONCLUSION: There 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.
Abstract: OBJECTIVES: The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients. METHODS: 36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study. TREATMENT: Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1-14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well. RESULTS: Most frequent related G3-4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3-4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0-15.7 months), the median response duration 2.8 months (95% confidence interval 1.2-5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7-6.3 months). The 1-year survival rate was 53.8%. CONCLUSIONS: The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC.
Abstract: Skeletal muscle metastases from lung cancer are rare, and the optimal treatment strategy is unknown. Three cases of skeletal muscle metastases from lung cancer are described. In 2 patients surgical biopsy of muscle swelling disclosed the presence of the lung tumor; the first patient underwent lung resection to remove the primary lesion, the second was not operable because of the metastatic extension of the disease. In the third patient muscle metastasis was observed and excised after lung resection. Adenocarcinoma, squamous cell, and small cell carcinoma were the histologic types diagnosed. Various regimens of radiotherapy and chemotherapy were adopted. Survival times were 3, 6, and 30 months.
Abstract: We present a rare case of renal cell carcinoma (RCC) with a metastatic, mainly osteoblastic lesion of the skull and spread to the lymph nodes. Renal tumors are often associated with bone metastases; these are most often of the osteolytic type, while osteoblastic metastases are extremely rare. In the case presented here, the primary metastasis was a large osteoblastic lesion of the skull that spread to the lymph nodes. The patient has undergone treatment for 20 months with interleukin-2: 3 million IU/day (subcutaneous) for six consecutive days once every four weeks, ie a total weekly dose of 18 million IU.
Abstract: PURPOSE: Colorectal cancer (CRC) is one of the major health problems of the Western world and the proportion of elderly patients with CRC is growing. Raltitrexed ('Tomudex'), a specific thymidylate synthase inhibitor, has shown efficacy and manageable toxicity in elderly CRC patients. In this retrospective study, the tolerability of raltitrexed in patients with CRC was examined in relation to age. PATIENTS AND METHODS: Toxicity parameters, graded according to World Health Organization criteria, were assessed in two patient groups: < 70 and > or = 70 years old. In total, 56% (50 out of 90) of patients treated with raltitrexed (3 mg/m2 as a 15-minute intravenous infusion every 3 weeks) were aged > 70 years (M:F 28:22; Eastern Cooperative Oncology Group performance status 0-1:2 38:12). RESULTS: Overall, 437 cycles of chemotherapy were administered and grade 3-4 toxicity was reported in < 10% of patients. There were no clinically significant differences between the two age groups, apart from grade 3-4 asthenia, which was reported by 6% and 0% of patients aged > or = 70 and < 70 years, respectively. This was in spite of a significantly lower calculated mean creatinine clearance in patients aged > or = 70 years compared with those patients < 70 years of age. CONCLUSION: The raltitrexed toxicity profile does not appear to be significantly influenced by age; however caution is recommended in the management of elderly patients, particularly in the presence of impaired renal function.
Abstract: BACKGROUND: Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are the main immuno-biological agents used in the therapy of metastatic renal cell carcinoma (RCC). Unfortunately the promising results obtained in biological studies have not yet been confirmed in clinical studies. One reason is linked to the immunosuppression of metastatic patients which is caused by macrophage products. IL-6 in particular is considered a growth factor for RCC. Medroxyprogesterone acetate (MPA) may interfere with IL-6 macrophage production, possibly causing a synergistic effect in association with IL-2 and IFN-alpha. Therefore the purpose of our study was to evaluate the toxicity and the efficacy of the association between IL-2, IFN-alpha and MPA. PATIENTS AND METHODS: Forty-two consecutive patients with metastatic RCC were enrolled. IL-2 was administered subcutaneously at doses of 4.5 million UI on days 1-5, 8-12, 15-19 and 22-26; IFN-alpha was administered s.c. at a dose of 3 million t.t.w; MPA was administered orally at a dose of 1000 mg daily. This schedule was repeated after a rest of 2 weeks. RESULTS: Toxicity was mild: the main symptoms observed were fatigue and fever. Six CR (14%), five PR (12%), thirteen SD (31%) and seventeen PD (41%) were observed for an overall response rate of 26%. Patients with good PS and low levels of CRP had a better prognosis. CONCLUSION: Considering both the good activity and the low toxicity of this scheme, we think that it could be carried out in normal clinical practice.
Abstract: The primary or secondary forms of colorectal cancers involving local structures or spreading in the abdomen or pelvic area without extra-regional metastases are identified as regionally advanced colorectal cancers (RACRC). They are unresectable and thus radiotherapy and chemotherapy are the fundamental treatment methods. However, these regimens have failed to check the diffusion of tumor satisfactorily in most forms of RACRC. The abdominal and pelvic regions can be isolated from corporal circulation by temporary occlusion of the aorta and cava and perfused with high doses of chemotherapeutic drugs. The hypoxic abdominal or pelvic stop-flow method for delivering high-dose antiblastic agents to these body districts to avoid toxicity by chemofiltration has been suggested. This study examines the possibility of using this method to treat various forms of RACRC.
