Primary non-Hodgkin's lymphoma of the female genital tract.

Genital tract lymphoma is a rare disease; information on diagnosis, treatment and outcome are limited. We report on eight patients affected by non-Hodgkin's lymphoma of the genital tract, five from the cervix, two from the vagina and one from the vulva collected between 1987 and 1998. Age at presentation ranged from 36 to 82 (median 67) years. The commonest initial symptom was vaginal bleeding, post coital in 1 patient. Three patients complained of vescical symptoms. Ann Arbor classification was stage IAE for 6 patients. Histology, according to the IWF, was either intermediate grade (4 patients), or high grade (3 patients), not evaluable in one case. Seven patients were treated with chemotherapy (anthracycline based in four) followed by pelvic radiotherapy in five; one patient received irradiation alone. Five patients are currently alive and free of disease with follow-up ranging from 8 to 126 months. Based on our experience in this series, we support a management scheme of combination chemotherapy and radiotherapy for patients with non-Hodgkin's lymphoma of the genital tract.

High-dose intensity cyclophosphamide, epidoxorubicin, vincristine and prednisone by shortened intervals and granulocyte colony-stimulating factor in non-Hodgkin's lymphoma: a phase II study.

Twenty patients with non-Hodgkin's lymphoma were treated with a combination of cyclophosphamide (750 mg m(-2), day 1), epidoxorubicin (60 mg m(-2), day 1), vincristine (1.4 mg m(-2), day 1) and prednisone (100 mg m(-2), days 1-5) every 14 days. Shortening of intervals was associated with the prophylactic employment of granulocyte colony-stimulating factor (G-CSF; specifically, filgrastim) administered at a dose of 300 microg subcutaneously from day 6 to day 11. The ratio between actually delivered dose intensity and planned dose intensity was 1.0 in 18 out the 20 patients. Toxicity was acceptable; response rate and survival are in the expected range. The present study demonstrated the feasibility of acceleration of chemotherapy cycles to obtain dose intensification in non-Hodgkin's lymphoma.

A phase II trial of carboplatin, methotrexate and fluorouracil in fluorouracil-pretreated colorectal cancer.

5-Fluorouracil and leucovorin combination is the most commonly applied chemotherapy treatment for colorectal cancer patients, both in the adjuvant setting and for advanced disease. Patients resistant or refractory to the 5-fluorouracil-leucovorin combination have been treated in this phase II trial with carboplatin plus methotrexate and fluorouracil in sequence. Twenty patients with measurable lesions from advanced colorectal cancer were entered in the trial. The treatment plan was carboplatin 300 mg/m2 day 1, methotrexate 40 mg/m2 day 1, fluorouracil 600 mg/m2 day 2, every 21 days. Two patients with liver metastasis had a partial response. Median survival was 12 months (range 4-24). Toxicity was acceptable and no patient had to be hospitalized because of the treatment. In this set of patients activity of the new combination is marginal.

A new schedule for etoposide, epidoxorubicin and cisplatin with granulocyte colony stimulating factor for advanced gastric cancer: a feasibility study.

A new polychemotherapy regimen has been developed for gastric cancer. Etoposide at the dose of 120 mg/m2 for three days, Epidoxorubicin at the dose of 30 mg/m2 on day 1 and Cisplatin at the dose of 40 mg/m2 on day 2 were administered to 26 advanced gastric patients every two weeks with the support of Granulocyte Colony Stimulating Factor from day 8 to day 12 of each cycle. The treatment was feasible with most cases (21/25) having received at least four cycles with a dose intensity > 85%, without life-threatening side effects. Toxicity was lower than that observed in the classical combinations of Etoposide-Anthracycline-Cisplatin.

Hypomethylation and hypoexpression of human CYP2E1 gene in lung tumors.

We have demonstrated the presence of CYP2E1 protein in a catalytically active form in lung tumors, differences being observed between the tumors and normal tissues from the same patients. Indeed, a higher microsomal CYP2E1 N-nitrosodimethylamine (NDMA) demethylase activity was present in normal tissues compared to tumors and was accompanied by corresponding change in CYP2E1 protein concentration, as shown by Western blot analysis. The catalytic activity among tumors differed from that among normal tissues with statistical significance of p < 0.01. CYP2E1 mRNA was present in lung tumors and less expressed compared to normal tissues from the same individuals. In order to understand the regulation of CYP2E1 gene expression, we studied the methylation status of the CYP2E1 gene in human lung tumors and normal tissues from the same patients and observed that a hypomethylation was associated with a hypoexpression of the CYP2E1 gene in lung tumors.

Tissue-specific expression and methylation of the human CYP2E1 gene.

The level and number of CYP2E1 gene transcripts were investigated by northern blot analysis in various human adult tissues including liver, lung, placenta, skin and neurinoma. Three transcripts of 1.8, 2.6 and 4 Kb were expressed in a tissue-specific manner. The origin of the various transcripts was studied and showed that both 4 and 2.6 Kb mRNAs contained sequences from the 3' non-translated region of the gene and that the 4 Kb also contained region localized in the 5' non-translated region. Furthermore, it clearly appeared that a catalytically active CYP2E1 enzyme (as proved by NDMA demethylase activity) was only detected in tissues expressing the 1.8 Kb. The human CYP2E1 was also identified through immunohistochemical techniques. Finally, we observed a relation between the hypomethylation of the human CYP2E1 gene and the hypoexpression of the corresponding protein.

[A proposal for the treatment technique for the breast and regional lymph nodes in patients with conservatively operated neoplasms]. / Una proposta tecnica per il trattamento della mammella e dei linfonodi regionali in pazienti affette da neoplasia operate conservativamente.

Adequate irradiation of regional lymph-nodes in selected patients seems to improve disease-free and over-all survival rates. Technically, regional lymph-nodes are generally treated separately (supra-infra clavicular, apex of axilla and internal mammary chain-IMC). About the treatment of the IMC nodes, there are two main problems: the identification of the individual target volume, and its correct irradiation. For the latter problem, the most employed solutions are: the inclusion of IMC in the tangential fields, the use of the direct or oblique electron beam for IMC alone. None of them is optimal regarding to the tolerance of adjacent critical organs and from a geometric and dosimetric point of view. In this paper we propose and discuss a modified method. The IMC nodes together with the breast are irradiated by a three field technique (two tangential photon beams and one oblique electron beam). Their arrangement allows to treat every part of the target by two fields, reducing the risk of hot and cold spots. This is obtained by extending the internal tangential photon beams to cover the electron beam. Wedges and different weights must be used to achieve an uniform dose distribution.

Impact of administration-related factors on outcome of adjuvant chemotherapy for primary breast cancer.

The survival of 229 patients treated with adjuvant i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after surgery for primary breast cancer was analyzed according to three administration-related factors: total number of cycles received, time elapsed between surgery and start of chemotherapy, and dose intensity of treatment. All parameters were found to be significantly associated with survival of patients in a univariate analysis. Multivariate analysis confirmed the independent prognostic importance of dose intensity and time between surgery and chemotherapy. Although prospective studies are needed to confirm such results, clinicians should be aware that unnecessary treatment delays or dose reductions in adjuvant chemotherapy for breast cancer are probably detrimental to patient survival.