Solitary breast metastases from a renal cell carcinoma.

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.

Mitomycin-C and lonidamine as second-line therapy for colorectal cancer: a phase II study.

AIMS AND BACKGROUND: Recent preclinical data have suggested that lonidamine may potentiate the acitivity of mitomycin C in human colon cancer cell lines LoVo and HT29. STUDY DESIGN: A phase II study was carried out in 14 patients with advanced colorectal cancer pretreated with fluorouracil and folinic acid. Treatment consisted of lonidamine, 600 mg po, followed after 2 h by mitomycin, 20 mg/m2 by iv bolus, followed by lonidamine, 150 mg tio for 5 days; the cycle was repeated every 6 weeks. RESULTS: No objective response was seen. Three patients had stable disease; the median survival for the whole group was 4 months. Although hematologic toxicity was negligible, lonidamine-related side effects were moderate to severe in most patients and mainly represented by myalgia and gastric pain. DISCUSSION: Despite a sound preclinical rationale, this schedule of lonidamine and mitomycin C was ineffective and toxic in patients with advanced colorectal cancer. More experimental data about lonidamine are needed in order to design more effective regimens based on the combination of this interesting drug with other anticancer agents.

MICE: a new active combination for non-small cell lung cancer.

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.

L-folinic acid and 5-fluorouracil in the treatment of advanced breast cancer: a phase II study.

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.

Fluorouracil, high-dose folinic acid, low-dose alpha-2b interferon and dipyridamole in the treatment of advanced colorectal cancer. A pilot study.

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.

A phase II trial of ProMACE-CytaBOM in previously untreated non-Hodgkin's lymphoma of intermediate- or high-grade histology.

Between November 1985 and June 1989 the aggressive combination chemotherapy programme ProMACE-CytaBOM was used at a community-based hospital as primary treatment for non-Hodgkin's lymphoma (NHL) of intermediate or high-grade histology in Ann-Arbor stages IB-IV. The 53 patients entering the study represented 90 per cent of all consecutive eligible patients with NHL diagnosed during the time period considered. Their median age was 54 years and median observation time was 36 months. Of 50 patients evaluable for response, 35 (70 per cent) achieved complete remission (CR), seven (14 per cent) partial remission, and five (10 per cent) were refractory. Treatment was given on an outpatient basis. Actually delivered drug doses ranged from 88 per cent to 97 per cent of the theoretical doses. Life-threatening toxicity was experienced by four patients. Treatment was stopped in three cases (6 per cent) because of toxicity and there was one treatment-related death. Actuarial 2-year disease-free survival of patients in CR was 73 per cent. Overall actuarial 3-year survival and disease-free survival were 67 per cent and 51 per cent respectively. High LDH level was a significant adverse prognostic factor both for achievement of CR (P less than 0.005) and for survival (P less than 0.0002). Age was of no prognostic importance. We conclude that ProMACE-CytaBOM is an effective, easy to administer and well-tolerated regimen for patients with aggressive NHL.

Mitomycin-C, adriamycin, 5-fluorouracil and leucovorin (L-FAM2) in the treatment of advanced gastric cancer: a phase II study.

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.

Mitomycin-C, vinblastine, and lonidamine as salvage treatment of advanced breast cancer. A pilot study.

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.

Phase II trial of 5-fluorouracil and high-dose folinic acid in advanced renal cell cancer.

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.

5-Fluorouracil and dipyridamole in metastatic breast cancer: a pilot study.

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.

Cyclophosphamide, epirubicin, high-dose folinic acid and 5-fluorouracil (super-FEC) as first-line chemotherapy for advanced breast cancer: preliminary results.

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.

Premarin priming before prednimustine, high-dose folinic acid and 5-fluorouracil as salvage chemotherapy for advanced breast cancer.

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.

Peptichemio, teniposide and high-dose dexamethasone: a new active combination for relapsing and refractory multiple myeloma. A pilot study.

Twelve patients with refractory (8 pts) and relapsing (4 pts) myeloma were treated with Peptichemio. Teniposide and high-dose dexamethasone. Eight patients experienced an objective response (5 out 8 with refractory and 3 out 4 with relapsing disease) with a median duration of 10+ months. Overall toxicity was mild to moderate and chiefly haematological. Our preliminary results seem very promising and justify a larger phase II study with this regimen.

Cisplatin, high dose folinic acid and 5-fluorouracil in squamous cell carcinoma of the esophagus. A pilot study.

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.

Cyclophosphamide, epirubicin and cisplatin (CEP) in advanced breast cancer: preliminary results.

Twenty-five patients with advanced breast cancer were treated every 28 days with Cisplatin, 30 mg/m2 iv on days 1,3,5; Epirubicin, 40 mg/m2 iv on day 1; Cyclophosphamide, 200mg/m2 iv on days 1,3,5. Partial remission was achieved by 7 patients (33%), all of whom had been untreated with chemotherapy. Overall toxicity was moderate but manageable. Severe haematological toxicity was experienced by 5 patients (20%) with grade III anemia; 2 patients had grade II oral mucositis; 4 had grade II diarrhoea Moderate nausea and vomiting were seen in all patients. Although they are only preliminary, our results suggest that this treatment had considerable activity as first line chemotherapy in advanced breast cancer and deserves further evaluation.

5-Fluorouracil and high-dose folinic acid as salvage treatment of advanced breast cancer: an update.

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.

Clinical experience with 5-fluorouracil (5-FU) and high-dose folinic acid in solid tumors.

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.