Biomedical subjects
Publications and source records attributed to P Marpicati.
A case of solitary and metachronous breast metastases from a renal cell carcinoma is described nine years after surgery. The review of the literature proves that the breast is an unusual site for metastatic disease.
We have treated 38 patients with stage III/IV non-small cell lung cancer with the following regimen: mitomycin-C = 6 mg/m2, ifosfamide = 3 g/m2, cisplatin = 75 mg/m2, vindesine = 3 mg/m2 (MICE), intravenously (i.v.) on day 1, every 3 weeks. Among 26 patients with stage IV disease, 15 obtained a partial remission (PR) (response rate = 57%, 95% confidence interval = 38-76), with a median time to disease progression and a median survival of 4.9 and 7.1 months, respectively. 6 out 7 patients with stage IIIA disease were documented as PR and 5 of them underwent radical surgery with two pathologically confirmed complete remissions. Overall toxicity was substantial but manageable: 3 patients had grade III/IV leucopenia (although 5 patients had neutropenic fever) whereas 13 patients experienced grade II/II anaemia. In conclusion we believe that MICE regimen is an interesting combination and warrants further evaluations both for palliation and in a neoadjuvant setting.
BACKGROUND: The combination of 5-fluorouracil (5-FU) and folinic acid (FA) is an active combination for the treatment of advanced breast cancer (ABC). Theoretically, the biologically active isomer of FA, 1-FA, should be more effective than racemic FA in modulating 5-FU activity. PATIENTS AND METHODS: Thirty-three patients (pts) with ABC, all previously treated with an anthracycline-based combination for advanced disease were treated with 1-FA: 100 mg/m2 i.v. and 5-FU: 370 mg/m2 i.v. for 5 consecutive days every 4 weeks. RESULTS: Three complete remission (CR) and 11 partial remission (PR) were obtained for an overall response rate of 42% (95% CI = 25-59). Median duration of response was 10 months, median survival was 15 months for responders, 11 months for NC and 3 for PD. Eleven pts experienced a WHO grade III-IV oral mucositis (33%), 6 pts had grade III and one grade IV diarrhea, two pts had grade IV neutropenia resulting in one toxic death. CONCLUSIONS: In this heavily pretreated population of pts with ABC, this regimen showed an interesting activity with substantial toxicity. Both the response rate and the pattern of side-effects seem similar to those experienced with the racemic mixture of d,1-FA. Modulated 5-FU warrants an increasing consideration in the treatment of breast cancer.
Thirty previously untreated patients with advanced measurable gastric cancer were given a combination chemotherapy consisting of 5-fluorouracil, 400 mg/m2, and leucovorin, 200 mg/m2 iv on days 1 to 3, mitomycin-C, 10 mg/m2 on day 1 (every other cycle) and adriamycin, 40 mg/m2 on day 2, repeated every 21 days. The overall response rate was 46% (14/30; 95% confidence limits: 28%-64%) including 4 patients with a complete remission. Eight patients progressed. Median duration of remission (CR+PR) was 10 months, with a median survival of 13, 8 and 4 months for CR+PR, NC and PD, respectively. Main toxicities were leukopenia (WHO grade III-IV in 36% of the patients) and alopecia. One patient died from myocardial infarction after an adriamycin cumulative dose of 480 mg/m2. No other treatment-related death occurred. L-FAM2 is an effective combination for advanced gastric carcinoma. Further studies based on the association of leucovorin and 5-fluorouracil in combination with other active drugs are warranted.
Twenty-six patients with advanced colorectal cancer were treated with a combination based on multimodal biochemical modulation of 5-fluorouracil by means of high dose folinic acid, low-dose alpha-2b interferon and dipyridamole. The overall response rate was 42% (95% confidence intervals = 23%. 61%) with four complete remissions (15%). The median duration of response was 9 months and the median survival for responders was 15 months (all patients = 12 months). Toxic side effects included oral mucositis (grade III-IV = 38%) and a generally mild flu-like syndrome. This regimen seems active and safe enough to be compared with the combination of fluorouracil and high-dose folinic acid.
Thirty-two patients with advanced breast cancer were treated with mitomycin-C 10 mg/m2 IV and vinblastine 6 mg/m2 IV every 21 days in combination with lonidamine 450 mg/day P.O. and prednisone 15 mg/day P.O. given continuously. Among the 29 evaluable patients (all but three pretreated with an anthracycline-based regimen), one complete remission (CR) and six partial remissions (PR) (response rate, 24%) were seen. The median duration of response was 14 months (range, 4-30 months). Median survival for responders was 18 months (range, 4-30 months). Hematological toxicity was uncommon; the main lonidamine-related side effects were myalgia, abdominal cramps, and reversible deafness; these side effects were severe in two, one, and one patients, respectively. The regimen seems to have a reasonable degree of activity and toxicity in advanced, refractory breast cancer. The role of lonidamine in the treatment of this disease warrants further evaluation.
Forty patients with metastatic breast cancer were treated with a new combination regimen consisting of cyclophosphamide, epirubicin, high-dose folinic acid and 5-fluorouracil (super-FEC). A major objective response was observed in 32 patients (80%). Among these, 11 patients (27%) experienced a complete remission. The median duration of response was 10+ and 12+ months for CR and PR, respectively. The most common side-effect was oral mucositis (Grade III = nine patients; grade IV = two patients), while haematological toxicity was virtually absent. Considering the high-risk characteristics of the vast majority of the enrolled patients (75% had dominant visceral disease), these preliminary results suggest that super-FEC has a powerful activity in poor-prognosis metastatic breast cancer with an acceptable degree of toxicity.
In an attempt to increase the clinical activity of 5-fluorouracil (5-FU) by blocking the thymidine salvage pathway, 15 patients with refractory metastatic breast cancer (MBC) were treated with oral dipyridamole (D): 75 mg p.o. q.i.d. and 5-FU: 400 mg/m2 i.v. by bolus for 5 consecutive days, every 28 days. All the patients were pretreated with 5-FU and an anthracycline-based regimen. Toxicity was minimal, with 8 patients experiencing a D-related moderate headache. Although no objective responses were seen, two patients with 5-FU refractory disease showed tumor shrinkage. A different D schedule and the addition of folinic acid (FA) to 5-FU might provide better results and deserves further evaluation.
Fourteen patients with metastatic renal cell carcinoma (RCC) were treated with high-dose folinic acid (HDFA): 200 mg/m2 i.v. and 5-fluorouracil (5-FU): 370 mg/m2 i.v. for 5 consecutive days every 28 days. Severe oral mucositis (WHO grade III-IV) was experienced by two patients, whereas hematological toxicity was mild. No complete or partial remission was observed. Short-lasting stable disease occurred in 8 patients (median = 5 months, range 2-11). This combination does not need further evaluation in patients with RCC.
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Thirty patients with advanced and mainly pretreated breast cancer were treated with a combination of premarin, prednimustine, high-dose folinic acid and 5-fluorouracil. Among the 30 evaluable patients, 9 (30%) achieved an objective response (median duration: 9 months). Oral mucositis was the limiting toxicity, while myelosuppression was quite mild. In spite of considerable activity as salvage regimen, these results do not seem better than those achieved in our Institute with high-dose folinic acid and 5-fluorouracil alone.
We report an update of our results of a trial of high-dose folinic acid (HDFA) and 5-fluorouracil (5-FU) in advanced breast cancer. Thirty-eight patients with advanced and mainly refractory breast cancer were treated with the following regimen: HDFA (200 mg/m2/day) and 5-FU (340, 370, 400 mg/m2/day) given immediately afterwards, for 5 consecutive days every 4 weeks. Of 36 evaluable patients, 3 achieved complete remission (8%) and 13 partial remission (36%) for an overall response rate of 44%, while 11 patients (30%) had stable disease. Thirteen out of sixteen responders (85%) were pretreated with some 5-FU-containing regimens. The median duration of response was 9.6+ months, the median survival for responders and for patients with stable or progressive disease was 19.9+, 18.8+ and 9 months, respectively. The overall toxicity was acceptable: while hematological toxicity was very mild, oral mucositis, diarrhea and conjunctivitis were major side effects. These results seem very promising and deserve further evaluation.
This paper reports experience with high-dose folinic acid (HDFA) and 5-fluorouracil (5-FU) in the treatment of 130 patients with various types of tumor. While the objective results obtained from gastrointestinal malignancies (response rate = 15%) are no better than those usually gained by 5-FU alone, impressive results were achieved in patients with advanced and mainly pretreated breast cancer (response rate = 44%). Haematological toxicity was generally mild, while oral mucositis, diarrhoea and conjunctivitis were major side effects. Our data suggest that HDFA and 5-FU seem a very promising combination and warrant further investigation.
We treated 20 patients with squamous cell carcinoma of the esophagus with the following regimen: cisplatin = 100 mg/m2 i.v. day 1, HDFA = 200 mg/m2 i.v. day 1 to 5, 5-fluorouracil = 370 mg/m2 i.v. day 1 to 5 repeated every 28 days. Among the 17 evaluable patients, 4 (23%) had a partial remission, 6 had stable disease while 7 progressed. The median survival for all patients was 6+ months. Grade III or IV toxicity included 2 patients with grade III leukopenia, 1 with grade III thrombocytopenia, 1 patient with grade IV and 3 patients with grade III oral mucositis, 3 patients with grade III diarrhea. The regimen did not seem particularly active in the treatment of squamous cell carcinoma of the esophagus and had manageable but substantial toxicity.
We studied estrogen and progesterone receptors (ER, PR) in 23 patients with chronic lymphocytic leukemia (CLL) and evaluated the results of this determination with other clinical and laboratory parameters. ER and PR activity was found respectively in 12 out of 23 (52%) and 6 out of 23 (26%) of the patients with a range between 2 and 23 fmol/mg protein (mean 10.3 fmol/mg) for ER and 18 and 92 fmol/mg (mean 41.8 fmol/mg) for PR. No correlations between ER/PR status and other parameters such as age, sex, stage, androgen and glucorticoid receptors (AR, GR), lymphocytic count or plasma estradiol and progesterone levels were noted. Seventeen consecutive patients out of 23 with a known receptor status and 1 with an unknown receptor status had been treated with tamoxifen 30 mg/day for 3 months. No objective response was achieved, despite some occasional reports of the literature.
Thirty-three patients with advanced breast cancer were treated with combination chemotherapy and hormonal synchronization in an attempt to increase the overall response rate generally obtained with traditional modalities of treatment. Among the 31 evaluable patients 1 complete (3%), 7 partial (22%), 13 stable disease (42%) and 10 progression of disease (53%) were obtained. Side effects were quite manageable although there were two episodes of life-threatening hematological toxicity. Taking into account the poor prognostic characteristics of our patients (high percentage of dominant visceral disease, 21/31 previously treated patients), our preliminary results with this regimen are interesting and the treatment deserves further evaluation.
We have investigated the activity of tamoxifen in 12 post-menopause patients affected by advanced breast carcinoma and, in this specific case, by metastatic pleural effusion. A receptor assay was carried out on all patients to assess the estrogen and progesterone receptor activity in pleural effusion tumor cells, cytologically confirmed. The assay was performed both at the moment of the diagnostic check and after a week of 30 mg/die of tamoxifen therapy. We obtained a temporary reduction of the pleural effusion in 5 patients out of 12 (42%). Four out of these 5 patients presented estrogen receptors (ER+) at the first assay. In the 4 patients with negative receptors (ER-) neither a decrease of the percentage of tumoral cells, nor a reduction of the effusion was ascertained. This study shows that also for pleural effusions tamoxifen's therapeutic benefit was obtainable only in those patients with estrogen receptors in the tumoral cells.