Gemcitabine and anthracyclines in platinum-resistant ovarian cancer.

BACKGROUND: Most of the patients with advanced ovarian cancer will recur after first-line platinum-based chemotherapy and need additional treatment. Gemcitabine (G) and Anthracyclines are active in this setting and their combination has shown synergistic antiproliferative activity in vitro, due to different mechanisms of action and non-overlapping toxicities. PATIENTS AND METHODS: In 2002 we began a phase II study with G 1000 mg/m(2) (day 1,8) combined to Epirubicin (E) 60 mg/m(2) (day 1), every 3 weeks for 6 cycles, in Platinum resistant/refractory ovarian carcinoma patients. RESULTS: Among 30 patients enrolled so far (27 evaluable), receiving 149 cycles (median 6), 1 complete and 12 partial responses (48%), 9 stabilizations (33%) and 5 progressions (18%) were observed, with a good correlation with serological responses. Median time to progression was 8 months, while median time to response was 10 weeks and median duration 8 months. Grade 3-4 toxicities consisted of neutropenia (58%), thrombocytopenia (3%), anemia (10%), liver toxicity (13%), and mucositis (7%). Eight patients (27%) received G-CSF and 3 (10%) blood transfusions. No febrile neutropenia nor cardiotoxicity were observed. CONCLUSIONS: Although our results are preliminary, G/E combination appears particularly effective and safe in these platinum resistant/refractory patients.

Induction therapy for squamous carcinoma of thoracic esophagus.

From June 1987 to March 1992, 70 patients with squamous cell carcinoma of the esophagus were entered into a treatment protocol that included a preoperative course of radiotherapy (3,000 cGy) and chemotherapy (cisplatin and 5-fluorouracil). The preoperative therapy was well tolerated. Forty-nine of these patients underwent esophageal resection (total or subtotal) and 6 patients died subsequently (12.2%). The morbidity was not dramatically affected by preoperative treatment. Histopathologic studies showed no residual disease in the resected specimen of 11 patients (19.2%), only some residual microscopic clusters of neoplastic cells in 8 patients (14%) and macroscopic cancer in the remaining patients (66.8%). The estimated overall Kaplan-Meier survival at 1, 2, and 3 years was 53.6%, 28.6%, and 21.5%, respectively. Our study, like other reports, demonstrates an improved survival in the group of patients who had a complete response after radiotherapy or chemotherapy (p = 0.002). Moreover, the lack of diagnostic procedures to evaluate the presence of residual tumor after radiotherapy and chemotherapy, suggests that only surgical resection can provide an accurate prognostic information and a complete treatment.

Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction.

AIMS: This study reports mode, timing and predictive factors of recurrence after curative surgery for cardia cancer. METHODS: A prospective study in a series of 92 curatively (R0) resected patients from 1988 to 2002. RESULTS: The 5-year recurrence rate was 71%. Lymph node involvement was the only predictor of recurrence. No patients with more than 6 metastatic nodes were free from relapse 2 years after surgery. Locoregional, peritoneal and haematogenous relapses showed a similar median recurrence time (12, 10 and 12 months, respectively), 80% occurred within 24 months. CONCLUSIONS: Few patients can be cured by surgery, lymph nodal involvement is the only predictor of recurrence.

Influence of radiotherapy on intestinal microflora in cancer patients.

We investigated in 15 patients with carcinoma of the uterine cervix or endometrium, who were undergoing postoperative radiation therapy, the effects of different fractionated radiation exposures on counts of fecal bacteria, on the growth of Clostridium difficile and Clostridium perfringens enterotoxin production. We observed a generally significant decrease in intestinal microflora after the first radiation exposure, whereas at the end of radiotherapy all bacteria increased and reached basal values except Enterococcus faecium 1, lactobacilli and total anaerobes. In some patients we observed an overgrowth of some Clostridium spp. which were potential pathogens associated with clinical symptoms. We did not observe an influence of multiple radiations on C. perfringens enterotoxin fecal contents. We conclude that patients receiving radiotherapy may benefit from the intake of oral bacteriotherapy, i.e. live beneficial bacteria such as Bacillus subtilis at the beginning of the irradiation exposure.

Kinetics of platinum in cancer patients treated with cisplatin at different doses.

In previous work the authors observed that platinum (free and bound) does not seem to accumulate in the peripheral compartment following the administration of two courses of cisplatin (cis-DDP) therapy (65 mg/m2) in patients with mammary and ovarian cancer. The aim of the present work was to study the disposition of platinum (Pt) after a higher dose of cis-DDP, to verify the rate of free drug penetration into the tissue and to observe changes in protein binding relative to the dose. cis-DDP, at the dose of 100 mg/m2, was administered i.v. over 60 min to patients with lung cancer. Serum and urine were collected before infusion and at various intervals afterwards. The plasma and urine levels of Pt were determined by flameless atomic absorption spectrophotometry, using a Varian model AAS 1475-GTA 95. Serum levels were analysed by a two-compartment open pharmacokinetic model. After the higher dose there was a substantial increase in central volume Pt and slight increase in peripheral volume Pt as compared with levels observed previously at the lower dose. In some subjects receiving high doses elimination half-life decreased and total body clearance increased, while in others these kinetic parameters were unchanged in comparison with those observed after a low dose. Protein binding seems to influence the persistence of platinum in the vascular space, modifying to a minor degree tissue penetration of the drug.

High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy.

BACKGROUND: This phase I study was aimed at defining the toxicity profile and pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant radiotherapy (RT) in locally advanced esophageal cancer. PATIENTS AND METHODS: The schedule consisted of a first phase of chemotherapy alone and a second phase of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20 mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29-49; RT (40 Gy) started on day 29. In the following steps the doses were escalated up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50 and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63 concurrently with RT 50 Gy. RESULTS: Forty-seven patients were enrolled and 46 completed the planned treatment. During the concomitant phase, grade 3-4 hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and non-hematological toxicities in six patients (13%) (or 7/179 cycles). A pathological downstaging was obtained in 59.6% of the cases (28/47): complete remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0) in eight patients, pT2 pN0 in three patients and partial response on the primary with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were considered stable and non-responders, respectively. In the last dose level, eight pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable dose was not formally defined because dose escalation was stopped at the last dose level. CONCLUSION: This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

Postoperative management of primary spinal cord ependymomas.

Treatment and final outcome of 11 patients with primary spinal cord ependymomas admitted between 1967 and 1983 have been reviewed. All patients had undergone surgery once or twice before radiation treatment. Six of them are alive and disease-free 78 months to more than 180 months after radiation therapy. A short analysis of the recent literature is presented with special emphasis on the most frequent treatment techniques, extension of radiation fields and doses. The value of postoperative radiation therapy and the complications of both surgery and radiotherapy are analyzed. Some guidelines for treatment are finally discussed and proposed.

Two-cycle cisplatin kinetics in patients with ovarian and mammary cancer.

The kinetics of platinum (Pt) in patients treated for two-cycle therapy with cis-DDP for ovarian or mammary carcinoma were investigated. Cis-DDP, at a dose of 65 mg/m2, was administered i.v. over 60 min to 6 patients every 3 weeks. Plasma was collected before and 1, 2, 4, 8, 24, and 48 h after the start of the first and second infusions. The levels of Pt in the patients' plasma were determined by flameless atomic absorption spectroscopy. Plasma levels were analyzed by a two-compartment open pharmacokinetic model. Plasma decline was biphasic, both after the first and the second cycle. In all patients, the calculated t1/2 of the rapid phase increased after the second cycle (from a mean value of 0.39 h to 2.45 h), whereas the t1/2 of the slow phase increased about threefold in 3 subjects. In the latter, we observed an increase of AUC and a decrease of total body clearance.

[Radiotherapy of brain metastases. Presentation of 104 cases examined by computerized axial tomography]. / Radioterapie delle metastasi cerebrali. Presentazione di 104 casi studiati con tomografia assiale computerizzata.

104 patients suffering from brain metastases and treated by whole brain irradiation have been studied with computerized tomography before and after radiation therapy. Brain computerized tomography is increasingly helpful and reliable in determining the location of metastases and regression of disease; it is too a more reliable source of information than neurologic examination in the evaluation of prognosis. Results of our study show that radiation therapy achieves an effective palliation and may be considered the most helpful therapeutic method of such patients; it really relieves symptoms relating to brain metastases and allows a longer survival in a fairly good number of patients.

[The problem of false positives in bone scintigraphy in patients with breast neoplasms. A follow-up at 10 years]. / Il problema dei falsi positivi ala scintigrafia ossea in pazienti con neoplasia mammaria. Verifica a 10 anni.

Bone scanning plays a pre-eminent role in tumor staging procedures, but its reliability is often questioned because of the high incidence of false positive results; not even bone biopsy can always clarify these questionable findings. To verify what actually becomes of the pathological hot spots lacking radiological evidence, we studied 49 patients with this discrepancy and followed them for an average period of 10 years (range: 8-11). The patients were divided into 3 subgroups: 1) 13 N+ patients with multiple hot spots (greater than 2) (N+ IM); 2) 24 N+ patients with single hot spots (less than or equal to 2) (N+ IS); 3) 12 N- patients with single hot spots (less than or equal to 2) (N- IS). Bone metastasis-free survival rate (SLMO) was calculated, which was confirmed by radiology, and overall survival rate (SG). SLMO was considered to coincide with the percentage of "true" false positives. At 10 years SLMO was 7%, 65%, and 83%, whereas SG was 15%, 70%, and 90%, respectively, in the 3 subgroups N+ IM, N+ IS, and N- IS. The Log-rank test demonstrated a highly significant difference (p less than 0.001) between SLMO and SG in these subgroups, due to the poor prognosis of N+ IM patients. The cumulative examination of all N+ N- patients with single hot spots (36 patients) demonstrated 75% probability of "true" false positives at 10 years. Moreover, the risk of bone metastases resulted higher in the hot spots of the spine than in those of the skull and ribs. The possible role is discussed of microfractures and bone traumatisms in the genesis of "true" false positives.

[Extracranial metastases from medulloblastoma: report of four cases (author's transl)]. / Metastasi extracraniche da medulloblastoma. Presentazione di 4 casi.

Four cases of bone and pulmonary metastases of medulloblastoma histologically diagnosed and with an exhaustive clinical-radiological and scintigraphic documentation, are described. In three patients, one of which non operated, the metastases of the osteolytic and osteoblastic type affected diffusely the skeleton; in the fourth patient the bone lesions were associated with a single pulmonary metastasis. The modality of metastatic spread and the clinical course of the illness in the diagnostic and therapeutic aspects are discussed.

Estrogen and progesterone receptors in breast cancer: correlation with clinical and pathological features and with prognosis.

Estrogen and progesterone receptor status was reviewed in 405 patients from prior adjuvant breast cancer trials at the University of Verona. Only 233 patients were actually examined with respect to hormone status and outcome. No relationship between hormone receptor status and most of the commonly followed prognostic signs, i.e. tumor size, nodal status, and age, was found. Overall survival was correlated with hormone receptor positivity for patients with more than 4 positive axillary nodes. Disease-free survival was correlated only with PgR positivity, in premenopausal and in T1 groups.

The antiemetic activity of high-dose metoclopramide and high-dose alizapride in combination with lorazepam in patients receiving cancer chemotherapy. A prospective, randomized, double-blind study.

The antiemetic efficacy of metoclopramide and lorazepam (MTC + L) versus alizapride and lorazepam (ALZ + L) was compared in 100 patients receiving chemotherapy, in a prospective randomized double-blind study. In highly emetogenic (HE) regimen (including platinum) patients received MTC 1 mg/kg or ALZ 3 mg/kg x 4 doses, and lorazepam 2.5 mg 30 min before therapy. In moderately emetogenic (ME) regimen patients received MTC 0.5 mg/kg or ALZ 1.5 mg kg x 3 doses, and lorazepam 2.5 mg 30 min before therapy. In both HE and ME regimen groups there was no statistically significant difference between MTC + L and ALZ + L treatments as regards the number of vomiting episodes, the duration of emesis and nausea, the intensity of nausea and side effects, but a statistically significant difference between treatments was found in the HE group where MTC-L was superior to ALZ + L in obtaining complete protection from vomiting (37 vs 11%, p = 0.05). No significant difference in side effects was observed.