A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma.

BACKGROUND: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. PATIENTS AND METHODS: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. RESULTS: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. CONCLUSION: Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit. CLINICALTRIALSGOV: NCT02409472.

Prognostic evaluation of patients submitted to surgery for malignant pleural mesothelioma.

The role of surgical resection remains controversial in malignant pleural mesothelioma. The assessment of its impact on prognosis is complicated by a poor understanding of the prognostic factors in the disease. We therefore evaluated, through univariate and multivariate analysis, the role on prognosis of 24 variables in 57 patients submitted to surgery from 1985 to 1993. Sixteen patients had only exploratory thoracotomy and 12 minimal residual disease after surgery (no nodules >1 cm in diameter). Thirty-four cases had epithelial histotype, 6 sarcomatous and 17 mixed. Median survival for the whole group was 15.7 months. Multivariate analysis showed a highly significant influence on survival for minimal residual disease after surgery (p=0.0006), followed by TNM stage (p=0.01). Median survival for patients with TNM stage I disease was 36.3 months and for patients with minimal residual disease 33 months. In conclusion, these data suggest that patients with limited disease have a longer survival after surgery than those with extensive disease. At the same time, our results indicate that the achievement of significant disease reduction with surgery has a critical impact on the prognosis of pleural mesothelioma.

Arterial chemoembolization with epirubicin in unresectable hepatocellular-carcinoma in cirrhosis.

No reliable therapy has yet been established for unresectable hepatocellular carcinoma (HCC). Encouraging data in terms of response rate and survival have been reported with intra-arterial chemotherapy combined with venooclusive materials, specifically ethiodized oil and gelatin sponge. To evaluate the activity and tolerance of a new chemoembolization protocol in cirrhotic patients with HCC, 22 patients were treated with epirubicin (50 mg) and ethiodized oil (10-15 ml), administered through hepatic arterial catheters, followed by gelatin sponge. Patient characteristics were: median age 70 years (range, 59-77); ECOG performance status 0-1 in 15 and 2 in 7 cases; Child's A disease in 11 and B in 11; TNM stage II in 9, stage III in 3 and stage IVA in 10 cases. Histologically documented cirrhosis was present in all cases. A total of 53 courses of therapy has been delivered. All patients were evaluable for response and toxicity. Three partial remissions (13%), 2 stabilizations of disease and 17 progressions have been observed. Median time to progression was 4 months, with a median survival of 7.6 months (range, 1-26+ months). Significant differences in survival (p = 0.001) have been observed between patients at stage II-III (21 months) and those at stage IVA (3 months), and between patients with Child's A disease (10 months) and Child's B disease (4 months) (p= 0.02). The treatment was well tolerated, with only 2 cases of WHO grade I pain and 2 cases of grade I fever. In conclusion, our results indicate that the schedule has only limited activity and does; not seem to offer any sure advantage over other treatments modalites in HCC.

Weekly vinorelbine in elderly patients with non-small-cell lung cancer.

AIMS AND BACKGROUND: Many lung cancers are diagnosed in patients over 65 years of age, but limited data are available on the tolerance and activity in elderly patients of chemotherapy protocols designed for adults. METHODS: We therefore activated a phase II study in patients aged 65 years or older affected by stage IIIB-IV non-small-cell lung cancer in order to assess the tolerance and activity of vinorelbine administered weekly at a dose of 25 mg/m2. RESULTS: Since June 1992, 25 patients (20 males, 5 females; performance status ECOG, 0-2) have been included in the study and are evaluable for response and side effects. Two-hundred and twenty-eight cycles of therapy have been delivered (median/patient, 9 cycles). Four partial remissions (16%; 95% confidence interval 5-36%), 9 disease stabilizations, and 12 progressions have been observed. Median time to disease progression was 3 months, and median survival was 5 months (range, 2-25+). Mild or moderate side effects included leukopenia (6 cases), neutropenia (4 cases), anemia (4 cases), nausea (4 cases), infection (3 cases) and thoracic pain (2 cases). Grade III/IV toxicity consisted mainly of leukopenia and neutropenia observed respectively in 5 and in 7 patients. No significant difference in terms of tolerability has been observed for patients aged 65 to 70 with respect to patients aged 70 years or older. CONCLUSIONS: The administration of vinorelbine in elderly patients does not seem to differ significantly in terms of response and tolerability from that recorded for adults. Selected elderly patients with good performance status and adequate organ function can be safely treated with systemic chemotherapy.

Medical treatment of hepatocellular carcinoma: any progress?

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common neoplasms worldwide. Curative treatment options include liver transplantation or resection. Unfortunately, most patients still have unresectable or untransplantable HCC due to disease extension or comorbid factors and are therefore candidate only for palliative treatments. METHODS: In this review we have analyzed the different medical approaches employed in the treatment of HCC in an attempt to better define their roles. RESULTS: Palliative medical treatments including systemic chemotherapy, immunotherapy or hormonal manipulation rarely influence survival of the patients. Although a high response rate is often reported with new local therapies such as transcatheter arterial embolization, intraarterial chemotherapy or percutaneous ethanol injection, the real impact of these treatment modalities on patient survival remains to be determined. CONCLUSION: One way to improve the diagnosis of HCC patients would be an appropriate approach to evaluate new drugs or treatment modalities. To answer all the open questions, further trials, possibly randomized, should be conducted on a substantial number of patients with homogeneous prognostic factors.

Pain at tumor site after vinorelbine injection: description of an unexpected side effect.

AIMS AND BACKGROUND: Vinorelbine is a new semisynthetic vinka alkaloid that has demonstrated good tolerability and interesting activity in a large spectrum of solid tumors. It was the aim of this paper to report the presence of a rarely documented side effect. METHODS: In our experience, 135 patients were treated with vinorelbine during the period 10/92 to 11/94 for a total of 1080 cycles. In 26% of the cycles, vinorelbine was administered in monochemotherapy and in 74% in polychemotherapy regimens. The dose of vinorelbine, administered in a weekly schedule, was 25 mg/m2 in 109 patients and 30 mg/m2 in 26 patients. In general, no analgesic premedication was used. Sixty-five patients had lung cancer, 45 had breast cancer, and 25 miscellaneous cancer. Only 4 patients had a previous history of neurotoxicity. RESULTS: Ten patients (7%) had pain in the tumor site within a few minutes of the vinorelbine injection. According to WHO grade, 5 cases had moderate and 5 severe pain. Pain was always reversible. In 5 cases ketorolac was administered after pain detection with resolution of the symptoms; in 4 cases it was necessary to deliver buprenorphine. One patient was admitted to the coronary unit because a myocardial infarction was suspected after retrosternal pain and required i.v. morphine. Seven cases refused to continue the treatment, and 3 cases had no further problem after ketorolac premedication. CONCLUSIONS: Although rare, the presence of severe pain after vinorelbine injection may adversely affect the treatment course. Such data are helpful in the recognition and management of this reversible side effect.

Surgery followed by intracavitary plus systemic chemotherapy in malignant pleural mesothelioma.

AIMS AND BACKGROUND: Malignant mesothelioma is associated with a median survival of 4 to 12 months. Data from the literature indicate that single modality treatment (surgery or intrapleural and/or systemic chemotherapy) does not significantly affect survival. METHODS: We therefore evaluated a combined approach consisting of surgery (pleurectomy + diaphragmatic or pericardial resection), intrapleural chemotherapy with cisplatin (100 mg/m2) and cytarabine (1,000 mg/m2) for 4 h immediately after pleurectomy, and systemic chemotherapy consisting of epirubicin (60 mg/m2) and mitomycin-C (10 mg/m2) day 1 every 4 weeks for 4 cycles. RESULTS: Twenty patients were enrolled in the study and were evaluable. Thirteen cases had residual gross disease after pleurectomy and 7 patients only minimal disease. Median time to disease progression was 7.4 months, and median survival was 11.5 months (range, 2-25+). No treatment-related death have been observed. Side effects after intracavitary chemotherapy included renal toxicity, anaemia and pain. Myelosuppression and alopecia were recorded during systematic chemotherapy. CONCLUSIONS: The results of the study indicate that the schedule is feasible, with encouraging results in terms of survival for patients with minimal residual disease after surgery.

[Aplastic anemia and myelodysplasia: a not-always-easy distinction]. / Anemia aplastica e mielodisplasia: una distinzione non sempre agevole.

The differential diagnosis between Myelodysplasia and Aplastic anaemia may be sometimes difficult, because clinical and morphological features may appear similar. Two cases, a Myelodysplastic syndrome with hypocellular and an Aplastic anaemia with hypercellular BM aspirates, are described in this report. Reciprocal connections between these two pathological entities, some biological aspects and the value of BM biopsy are also discussed.

Mitoxantrone, fluorouracil plus L-leucovorin, and vinorelbine in pretreated advanced breast cancer.

The combination chemotherapy including mitoxantrone, fluorouracil and leucovorin has proven to be effective and well-tolerated in advanced breast cancer (ABC). No data are available on the association with navelbine, a new vinka alkaloid, which has demonstrated high activity in ABC. The trial was designed to evaluate feasibility and efficacy of the association of vinorelbine to mitoxantrone, fluorouracil and L-leucovorin in patients who failed a previous regimen for ABC or who relapsed within 6 months of adjuvant chemotherapy. The schedule was as follows: mitoxantrone 6 mg/m2 days 1 and 8; L-leucovorin 250 mg/m2 days 1 and 8, fluorouracil 600 mg/m2 days 1 and 8, vinorelbine 25 mg/m2 days 1 and 8, cycles being repeated every 21 days. Twenty-five patients were enrolled and are evaluable for response and side effects. One hundred cycles of therapy have been delivered (median/patient, 4 cycles). In 41 cycles a delay was required and in 38 cycles it was necessary to administer granulocyte colony-stimulating factor for neutropenia. Seven partial remissions (28%; 95% confidence interval, 12-49%), 10 stabilizations of disease and 8 progressions were observed. Although grade 4 neutropenia was observed in 44% of the patients, no grade 3-4 infections were observed. Nonhematologic toxicities were mild or moderate and included alopecia, mucositis and phlebitis. In conclusion, the schedule employed, although correlated with a moderate activity, does not seem to be superior to other regimens with mitoxantrone, fluorouracil, and leucovorin.