A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

BACKGROUND: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. RESULTS: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). CONCLUSIONS: In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.

Mitomycin C and etoposide in advanced colorectal carcinoma. A clinical and in vitro experience that focuses the problem of schedule dependence in combination therapy.

BACKGROUND: Aim of this study was to evaluate the activity of a combination regimen of chemotherapy containing mitomycin C (MMC) and etoposide (ETO) in advanced colorectal carcinoma. METHODS: Fourteen pretreated patients received MMC 2 mg/m2 and ETO 60 mg/m2, days 1-5 every 28 days. The clinical study was interrupted since no clinical response was observed in 14 patients following four courses of chemotherapy. An in vitro study was then performed on HTC-8 cell line. The cytotoxic activity of the MMC/ETO combination was tested by sulforhodamine B assay and the type of drug interaction was assessed using the method of Chou and Talalay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. RESULTS: While MMC and ETO were singularly active, the simultaneous exposure of cells to both drugs and the sequence MMC-->ETO ensued in antagonistic interaction at all levels of killed cell fraction. Conversely, the sequence ETO-->MMC produced a synergistic interaction. CONCLUSIONS: These results suggest that the activity of the MMC/ETO combination is highly schedule-dependent and that the experimental drug associations should be based on a preclinical rationale before clinical trials are designed.

Elevated doses of carmustine and mitomycin C, with lonidamine enhancement and autologous bone marrow transplantation in the treatment of advanced colorectal cancer: results from a pilot study.

10 patients with advanced colorectal cancer were treated with elevated doses of carmustine and mitomycin C. The regimen was potentiated by lonidamine and supported by autologous bone marrow transplantation. The results of this pilot study were encouraging, with a response rate of 50% and a significantly better survival for responders versus non-responders. No appreciable toxicity of the therapy was observed. This aspect, together with the simplicity of the procedure, calls for further investigations to confirm the good therapeutic index of the treatment.

A new anthracycline regimen for prolymphocytic leukemia? Study of a case report with flow cytometric implications.

A case of prolymphocytic leukemia (PL) is reported, which showed a good response to a new antiblastic schedule (4-epidoxorubicin-asparaginase-dexamethasone) in spite of the resistance to other chemotherapy regimens. However during the course of the disease it was possible to observe the terminal appearance of a small aneuploid cell population in the peripheral blood of the patient and, in the same time, the clinical condition deteriorated considerably. The significance of this neoplastic progression and the pros and cons of aggressive chemotherapy regimens remain to be carefully evaluated in PL and related disorders.

High-dose chemotherapy with bone marrow transplantation for advanced colorectal cancer.

A chemotherapy regimen based on high doses of BCNU and mitomycin C with autologous bone marrow transplantation was used in 18 patients with advanced colorectal carcinoma. Haematological toxicity was manageable, with a short nadir for white blood cells and platelets. The response rate was 33%, with a prevalence in peritoneal lesions compared to liver or lung metastases. Extra-haematological toxicity appeared in 16% of cases: a case of veno-occlusive disease of the liver and two cases of lung impairment are discussed. Although the response rate obtained with the regimen was satisfactory, the more extensive use of high-dose chemotherapy followed by autologous bone marrow transplantation requires the identification of less toxic protocols.

Aneurysm arising from the medial branch of the superior cerebellar artery.

A case is presented of an aneurysm arising from the distal portion of the medial branch of the superior cerebellar artery. The aneurysm was discovered after a subarachnoid hemorrhage and was clipped successfully. We found no similar distally located aneurysm in a review of the literature. The close relationship between the superior cerebellar artery and the posterior cerebral artery is discussed to facilitate the proper choice of surgical approach.

Effect of energy substrate manipulation on tumour cell proliferation in parenterally fed cancer patients.

The effects of isocaloric carbohydrate-based vs. fat-based total parenteral nutrition (TPN) regimens on cancer cell proliferation and host nutritional status were evaluated in 27 patients with tumours of the gastro intestinal tract consecutively assigned to receive for 14 days: a glucose-based (A) or a lipid-based (B) TPN formula, or an oral diet (C) isocaloric and isonitrogenous to A and B. Cancer cell replication rate was evaluated by thymidine labelling index (LI) on tumour samples before and at the end of each nutritional regimen. The number of replicating cells increased by 32.2% in patients receiving regimen A. LI decreased by 24.3% in patients given regimen B. LI values were slightly increased (+15%) in patients maintained on regimen C. Nutritional status remained within normal limits. None of the LI changes observed between and within the three arms of the trial were found to be statistically significant. Thus we failed to prove that glucose consistently stimulates or lipids inhibit tumour proliferation despite a trend in this sense.

Alternating intravenous courses of melphalan and peptichemio in high-risk multiple myeloma (preliminary results).

Six patients with high-risk multiple myeloma and one patient with primary amyloidosis were treated with a melphalan-peptichemio-prednisone association (PMP). The response trend seems promising, also in view of the low regimen bone marrow toxicity, but further studies could better evaluate the optimal PMP scheduling and peptichemio side effects.

Long-lasting response to vinorelbine in unresectable non-small cell lung carcinoma: a case with concomitant good quality of life.

The authors observed a long-lasting response to uninterrupted vinorelbine treatment in a 72-year-old patient with a stage IIIB unresectable non-small cell carcinoma. The progressive tumor mass reduction was assessed by computed tomographic scans over a 2-year period. In the literature, data of randomized trials confirm that the appeal of single-agent vinorelbine therapy in elderly patients is also good for the patient's quality of life during treatment.

The surgeon's decision as a prognostic factor in a pool of patients with colorectal cancer coming from different institutions.

Different pathological and predictive factors are used to stratify patients submitted to radical surgery for colorectal carcinoma. In addition to stage and histotype, the surgeon's technique and decisions also appeared to affect the prognosis. The aim of the present study was to evaluate if the extent of lymphadenectomy was associated with a different long-term outcome in a pool of 117 patients. In particular, in patients classified as Dukes' B, some evidences seem to suggest that the staging procedure depends on a correct surgical lymphadenectomy with a higher risk of understaging colorectal carcinomas when the number of removed nodes is limited. Moreover, the promptness in forwarding patients to the chemotherapist seems to influence the disease-free survival.

Nucleotide fractional incorporation: a simple metabolic feature potentially related to clinical outcome in colorectal cancer patients.

Among the different investigated biomarkers, cell proliferation has provided valuable information on the clinical outcome of patients with malignant tumors. In the present study, we analyzed the potential relevance of fractional incorporation (FI) of a nucleotide precursor (3H-thymidine, 3H-dT) into DNA of tumor cells, determined on the primary tumor, on long-term clinical outcome of a series of patients with colorectal cancer. Determination of 3H-dT FI was carried out on fresh tumor material obtained at surgery as part of the clinical management of the primary tumor in 28 patients with colorectal cancer. Analysis of the relation between the FI and clinico-pathological characteristics of the tumor showed a trend of an inverse relation between the biomarker and Dukes' stage and no relation with tumor site. At 6 year follow-up, alive patients had a statistically significant higher median FI value (2.4%; range: 1.1-6.5%) than dead patients (1%; range: 0.3-4.5%) (p=0.02). Owing to the simplicity of this inexpensive methodology, the preliminary results of our study would indicate the potential of FI, a metabolic-kinetic parameter, to give prognostic information in colorectal cancer patients.

Restoration of immune functions after chemotherapy.

A paradigmatic case in which anticancer chemotherapy could paradoxically lead to immune restoration is reported. A patient with hairy cell leukemia was unsuccessfully treated with alpha-interferon. Treatment had to be withdrawn because of unusual toxicity and therapy with cytotoxic drugs had to be administered. Not only did the anticancer agents produce a complete remission of the disease, but the immunological profile of the patient improved. This case report raises the problem of the interference of chemotherapy with the immune system in cancer patients.

T and B lymphocytes: two different cell populations for the "first defence barrier" at cutaneous and mucosal levels?

Data on lymphocyte biology indicate that the humoral system of B-cells is specifically active with precise analogies at all mucosal levels. Might there be a corresponding function for T-lymphocytes at the cutaneous structure level? Certain physiological findings appear to suggest that the two main lymphocyte populations share the role of "first defence barrier".

Chronic neutrophilic leukemia and myeloma. Report on long survival.

A case of chronic neutrophilic leukemia associated with multiple myeloma is described. The patient appears to be the longest surviving case reported in the literature. Since myeloma developed several years after leukemia, the possible precancerous role of myeloproliferative syndromes is proposed.

Cancer-associated hemolytic-uremic syndrome with spontaneous resolution. A case report.

A case of cancer-related hemolytic-uremic syndrome is reported. The patient presented a spontaneous recovery, which is unusual in this clinical picture. Mitomycin C is regarded as responsible for this toxic event in most cases. The case history reported here is discussed in relation to dose and scheduling of mitomycin C, and a safe maximum dosage is suggested.

Drug sensitivity of different tumor lesions from the same patient evaluated by a short-term assay.

A short-term antimetabolic assay, which considers the interference with [3H]thymidine incorporation as an indicator of drug effect, has been used to comparatively assess the chemosensitivity of different tumor lesions from the same patient. The analysis was performed on primary tumors and their synchronous metastases from 67 patients with breast, ovarian, gastrointestinal and germ cell testicular tumors. A remarkable difference in sensitivity to cytostatic drugs was observed between the two lesions. In contrast, a strong association in chemosensitivity (81.7% agreement rate; p less than 0.01) was observed between two synchronous metastases from 17 patients with breast, ovarian, germ cell testicular tumors or malignant melanoma. In addition, the predictive relevance of the antimetabolic assay on clinical response to chemotherapy was analyzed in relation to the type of tumor lesion tested in vitro in a retrospective correlative study on 57 patients with advanced ovarian and germ cell testicular tumors. The objective clinical response was significantly correlated to the in vitro sensitivity of metastases (83.7% agreement rate; p less than 0.01), but not to that of the primary tumor.

Anthracycline in colorectal carcinoma: an in vitro short-term assay to predict drug sensitivity. Preliminary results.

The chemosensitivity of 26 non-pretreated colorectal carcinomas (primary tumors and/or colorectal metastases) was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. Our results correlate with the response rate obtained in clinical studies with monochemotherapy and justify the possibility of a future prospective study using individually tailored chemotherapy regimens. Doxorubicin-analogues, with an overall in vitro efficacy in 16.0% and 14.3% for 4-epidoxorubicin (epi-DX) and 4-deoxydoxorubicin (deo-DX), respectively, seem to deserve a modest role in the treatment of colorectal cancer, provided that a careful selection of patients is performed. Variability in anthracycline activity is indeed evident, also in our study, in relation to the different neoplastic picture of the various patients.

Comparative in vitro and in vivo study of a nitroxyl derivative of 5-fluorouracil (magnizil) on human gastrointestinal tumors.

AIMS AND BACKGROUND: There is much interest in nitroxyl derivatives of cytotoxic agents. We evaluated the potential activity of magnizil, a derivative of 5-fluorouracil, on human gastrointestinal tumors in 3 different in vitro and in vivo experimental models. METHODS: The activities of magnizil and 5-fluorouracil were comparatively determined in vitro on the HT29 cell line by a clonogenic assay and on tumor clinical specimens by an antimetabolic assay. The activity of both the drugs against human tumors was also assessed in mice with the subrenal capsule assay. RESULTS: A similar cytotoxic activity was found for magnizil and 5-fluorouracil on the HT29 cell line. As regards human tumors, a lower activity was observed for the nitroxyl derivative than for 5-fluorouracil, with response rates of 25% and 50%, respectively, at comparable concentrations. Moreover, among the tumors transplanted in the subrenal capsule of mice, two were sensitive to magnizil and 3 to 5-fluorouracil. CONCLUSIONS: Even though experimental results on human tumors indicate a somewhat lower activity for magnizil than the parent compound, its low toxicity and the possibility to clinically use high doses suggest the opportunity to further investigate the potential of this new anticancer agent on larger series of colorectal cancers in experimental systems.

Failure of imaging techniques in revealing breast cancer progression.

This study focuses on a case of a 67-year-old woman with occult breast cancer involving the axillary lymph nodes. The instrumental examinations employed, positron emission tomography included, were not useful in diagnosing the disease. When the patient was surgically treated micro-invasive breast cancer was diagnosed. This peculiar malignant pathology is a matter of discussion especially because it is hardly diagnosable. Because of such diagnostic difficulties it may happen that micro-invasive carcinoma progression can easily mislead routine diagnostic screenings performed on women over 50.

Intrarticular methotrexate in the therapy of rheumatoid arthritis.

Five patients with oligoarticular rheumatoid arthritis were treated with intra-articular injections of methotrexate and orgotein in the knee joints. The employed dose of the antimetabolite was very low and orgotein was simultaneously administered to prevent local tissues from cytolysis-related damage. Clinical results were fairly good and support the hypothesis that methotrexate may be used intra-articularly as an immunosuppressor rather than at the heavily toxic doses required for a cytostatic effect.