A Randomized Study of Epithelial Ovarian Cancer: Is Chemotherapy Useful after Complete Remission?

Objective. The aim of this study is to verify whether consolidation chemotherapy with Cisplatin improves disease-free survival and/or overall survival in patients affected by epithelial ovarian cancer.Methods. A multicenter study examined 122 randomized patients in complete remission as judged by laparoscopy or laparotomy following first-line chemotherapy consisting of ACy (Adriamycin + Cyclophosphamide), PCy (Cisplatin + Cyclophosphamide), or Mitoxantrone + Carboplatin. Sixty-one of these patients were treated with 3 cycles of 5-Fluorouracil (FU) 500 mg/m2 for 5 days followed by Cisplatin at 100 mg/m2 on the 6th or 7th day every 28 days; the other 61 received no further treatment (nihil group).Results. Sixty patients in the Cisplatin arm were evaluable. There were 36 relapses in the FU+Cisplatin arm and 30 in the nihil arm. Peritoneal relapses were 25% for Cisplatin treatment vs. 16.4 % for nihil. There were 29 deaths in the Cisplatin arm vs. 27 for nihil. Median overall survival time (95 months with Cisplatin vs. 96 months in the nihil group) and median disease-free survival (66 months with Cisplatin vs. 73 in the nihil group) were similar in both arms (p=0.66 and p=0.41, respectively). There were no significant differences in tumor stage and grade between the two arms. Seven patients presented a second neoplasm during follow-up: six in the nihil arm, but only one patient in the Cisplatin arm. Death in these patients was due to the second neoplasm and not to progression of ovarian cancer.Conclusion. Three courses of additional platinum+FU treatment after five cycles of first-line chemotherapy without FU produced no increase in overall survival or disease-free survival.

Procarbazine and high-dose tamoxifen as a second-line regimen in recurrent high-grade gliomas: a phase II study.

PURPOSE: A phase II study was conducted in patients with high-grade gliomas that recurred after surgery plus radiotherapy and a first-line nitrosourea-based regimen. Our aim was to investigate the efficacy of procarbazine (PCB) combined with high-dose tamoxifen in relation to tumor control, toxicity, and time to progression (TTP). PATIENTS AND METHODS: Fifty-three patients were treated with procarbazine in repeated 30-day courses at 100 mg/m2/d plus tamoxifen 100 mg/d, with a 30-day interval between courses. Thirty-four patients had been pretreated with a first-line nitrosourea-based chemotherapy regimen (group A), and 19 patients had also been pretreated with a second-line chemotherapy regimen consisting of carboplatin and teniposide (group B). Twenty-one of the patients had also been procarbazine pretreated, whereas the remaining 32 patients were not procarbazine pretreated. RESULTS: The response was assessed in 51 patients, 28 of whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma (AA). There were two complete responses (CR) (4%) and 13 partial responses (PR) (25.5%). The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence interval [CI], 23 to 35.8). Seventeen patients (32%) had stable disease (SE, 6.2; 95% CI, 21 to 33.6). The median TTP was 13 weeks for patients with GBM and 33 weeks for patients with AA (P = .006). The median survival time (MST) was 27 weeks for patients with GBM and 57 weeks for those with AA (P = .006). CONCLUSION: Combined PCB and tamoxifen as a second-line regimen gave a reasonably high response rate in patients with heavily pretreated high-grade gliomas. However, although it resulted in an improvement in the patients' quality of life and/or performance status, it was not followed by an increased TTP or MST.

Unusual nasal and orbital involvement of glioblastoma multiforme: a case report and review of the literature.

We describe a case of glioblastoma treated with chemoradiotherapy that spread to the dura mater with direct invasion of the skull base, protrusion into the homolateral nasal fossa, and penetrated of the frontal sinus, the orbital wall and the ethmoidal sinuses. Only eight cases of glioblastoma showing this development have been described in the literature; one of these, however, had a sarcomatous component which was absent in our case.

Treatment of high-grade gliomas in the elderly.

In recent years the elderly population has grown, and in this category there has been a marked increase in the incidence of cancers with a poor prognosis, brain tumors in particular. However, few authors have focused on treatment for high-grade gliomas in the elderly, which often present problems different from those in younger populations. Several authors have observed that this tumor has a poor response to surgery, radiotherapy and chemotherapy. Elderly patients are therefore frequently undertreated or excluded from cancer therapy trials. Their exclusion from conventional cancer treatment often depends on ad hoc decisions and assumptions by physicians rather than on sound scientific data.

Incidence of risk of thromboembolism during treatment high-grade gliomas: a prospective study.

A prospective study of a series of 77 patients on adjuvant radiochemotherapy following surgery for high-grade gliomas was conducted to evaluate the risk of deep vein thrombosis and identify risk factors. We found a 20.8% risk of deep vein thrombosis at 12 months (standard error = 4.8%) and a 31.7% risk (standard error = 7.4%) at 24 months (Kaplan-Meier method). Twenty patients (26%) developed deep vein thrombosis with a maximum incidence within the first 7 months after surgery when chemotherapy was still being administered, often with corticosteroids. The risk factors identified were histology (glioblastoma versus anaplastic astrocytoma, P = 0.032, log rank test; 0.0485 L-ratio) and the presence of paresis (P = 0.010, log rank test; 0.0161 L-ratio). A borderline tendency was found for an association between the deep vein thrombosis site and the side of paresis (P = 0.103, Fisher's exact test). Four patients (5%) had massive pulmonary embolism, which was fatal in 3 (4%).

Phase II trial with BCNU plus alpha-interferon in patients with recurrent high-grade gliomas.

A Phase II study with a combination of BCNU and alpha-interferon (IFN) was conducted in patients with high-grade glioma recurrent after surgery and radiation treatment in order to investigate tumor control and toxicity. Twenty-one non-chemotherapy pretreated patients were administered 6 MU alpha-IFN in a 2-h infusion followed by 150 mg/m2 BCNU i.v. on day 1. Three MU alpha-IFN were subsequently administered subcutaneously on alternating days three times a week, until recycling of the whole procedure on day 42. Among 21 patients, partial remission was obtained in 7 (33%; 95% CI = 15-57) and stable disease in 6 (29%; CI = 11-52); overall Kaplan-Meier median time to progression (TTP) was 4.5 months (CI = 4-9) and the overall median survival time (MST) was 7 months (CI = 5-13). In patients who underwent surgical redebulking prior to chemotherapy, TTP and MST were 9 (CI = 7-14) and 15 months (CI = 11.0-39.0); in patients who were not operated on again before chemotherapy, these values were 4 (CI = 2-5; log rank test, p = 0.0026) and 5.5 months (CI = 4-7; log rank test, p = 0.0012) respectively. The results of this regimen in relapsing patients, especially following surgical redebulking, are encouraging; toxicity is acceptable, and further studies on combined alpha-IFN and multiple-agent chemotherapy are warranted.

Surgical second look in ovarian cancer: a randomized study in patients with laparoscopic complete remission--a Northeastern Oncology Cooperative Group-Ovarian Cancer Cooperative Group Study.

PURPOSE: The usefulness of extensive and repetitive surgery for patients with ovarian cancer still remains unproven (at least for some conditions). We planned an accurate prospective test of the hypothesis that patients with advanced-stage disease, after they had reached a clinical complete remission (CR), may benefit from surgical second look (SSL). PATIENTS AND METHODS: One hundred two patients in CR (as assessed by clinical findings, markers, and visualization by computed tomographic [CT] scan and laparoscopy), after initial debulking and first-line chemotherapy, were randomized to two arms, which were well balanced for predictive criteria such as age, stage at presentation, histology, grading, date of randomization, and residua after first surgery. Forty-eight patients were randomly assigned to receive follow-up evaluation only, while 54 were assigned to receive second surgery (eight of them refused). Of 46 surgical patients, 35 had negative and 11 positive surgical findings (24% clinically false-negative). RESULTS: Despite the microscopic residua found at open surgery, and the fact that the patients were then treated with second-line chemotherapy, SSL did not increase the probability of survival in this setting. In an analysis of the results according to the intention-to-treat criteria, after a 60-month follow-up period, the overall survival rates in the two groups of patients (SSL v no SSL) were 65% and 78%, respectively (P = .14). Multivariate analysis according to predictive criteria confirmed there was no significant difference between the two groups (P = .39). CONCLUSION: Our study shows the following: (1) our second-line treatment is scarcely effective; (2) SSL accurately defines complete responders to first-line chemotherapy; (3) SSL per se does not prolong survival; and (4) if confirmed, a less invasive procedure could replace SSL as a valuable method in new first-line regimens in ovarian cancer patients with clinical CR confirmed by laparoscopy.

Early chemotherapy and concurrent radio-chemotherapy in high grade glioma.

PURPOSE: The poor results from treatment of high grade glioma prompted us to explore new protocols involving concurrent radio-chemotherapy. Our primary objective was to evaluate the feasibility of very early postoperative chemotherapy with BCNU, concurrent radio-chemotherapy with carboplatin and teniposide, and post-radiotherapy BCNU. Our secondary objectives were to evaluate time to progression, and overall survival. PATIENTS AND METHODS: We treated 24 newly diagnosed patients (pts) with BCNU 150 mg/m2 seven days after surgery. Thirty days later, we started radiotherapy, 1.8 to 2 Gy/day for 5 days a week on limited fields up to 60 Gy, and concurrent chemotherapy with carboplatin 250 mg/m2 on days 1, 22, and 43, and teniposide 50 mg/m2 on days 1, 2, 3, 22, 23, 24, 43, 44 and 45. Two cycles of 150 mg/m2 BCNU were then given at 30 and 70 days, respectively, after the end of the radio-chemotherapy course. Therapy was then suspended, but if disease progression was evident, treatment was resumed with drugs that had not been previously employed. Surgical reintervention was not routinely considered. RESULTS: Following radio-chemotherapy treatment in the 24 pts evaluable for response, we observed partial remissions in 8 cases (33%) and stable disease in 12 (50%). Actuarial estimates of progression free survival (PFS) were 33 weeks, with 56 wks for anaplastic astrocytoma and 31 weeks for glioblastoma. Median survival time (MST) of all pts was 58 weeks; 51 weeks for glioblastoma and was not reached for anaplastic astrocytoma. This regimen was feasible. Of 144 planned cycles, 139 were delivered, and among these only in 13 and 9 cycles the doses were reduced by 75 and 50%, respectively. We did not observe any gastrointestinal toxicity. Grade 2 hematological toxicity occurred in 25% of pts. grade 3 in 4% and neurological toxicity in 3% of the pts during BCNU delivery, probably due to a sharp increase in intracranial pressure. CONCLUSION: Early chemotherapy, concurrent chemo-radiotherapy and brief post-radio-therapy chemotherapy are feasible and well tolerated. The objective response and disease stabilization rates appear similar to previous experiences.

Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients. Feasibility, toxicity and long-term results of a phase II study.

The aim of this study was to evaluate the feasibility, the response rate and the effect on survival of full dose polychemotherapy delivered concurrently with bifractionated radiotherapy at a radical dose, in a subset of patients with marginally resectable or unresectable stage IIIA-B non-small cell lung cancer (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m2 for 1 day plus etoposide 120 mg/m2 for 3 days delivered from day 1 to day 22, plus radiotherapy delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to 33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal fractions. After surgery, three additional courses of cisplatin plus etoposide were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC (19 were judged as having marginally resectable, 20 as having unresectable disease) were entered into the study. Out of 39 patients (22 squamous cell carcinoma, 17 adeno/large cell carcinoma), 24 had stage IIIa (62%) and 15 stage IIIb (38%). Median PS was 80 (70-90). A total of 78 (74 evaluable) concurrent cycles of pre-operative chemoradiotherapy were delivered. The prominent side-effect was leucopenia: leucopenia > or = grade 3 at nadir occurred in 20 cycles (27%), thrombocytopenia > or = grade 3 at nadir in seven cycles (9%), 19 patients (54%) had a treatment delay of 1 week between the two cycles. Other important toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR (complete response), 16%; 19 PR (partial response), 51%). A resection was subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%) macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5 relapsed locally and 11 only distantly. At present, with a follow-up ranging from 64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4 (17%) are alive without evidence of disease. Median survival was 16 months, with 18% 3-year survivors and 13% 5-year survivors. Resected patients had a median survival of 21 months, versus 10 months for unresected patients (P = 0.01). No significant difference was evident between stage IIIa and stage IIIb patients.

Mitomycin C, vinblastine, and carboplatin regimen in patients with nonsmall cell lung cancer. A phase II trial.

BACKGROUND: The mitomycin C, vinblastine, and cisplatin (MVP) combination is one of the most frequently used in the palliative setting, but it produces considerable toxicity. Carboplatin and cisplatin have different patterns of toxicity. The goal of this study was to evaluate a combination similar to MVP, using carboplatin instead of cisplatin to render it more feasible in an outpatient setting. METHODS: Inclusion criteria for this study included: inoperable patients or patients relapsing after previous surgery, with nonsmall cell lung carcinoma (NSCLC), a performance status (PS) > 50%, and no previous chemotherapy. The chemotherapy regimen included carboplatin, 300 mg/m2 on Day 1; mitomycin, 8 mg/m2 on Day 1; and vinblastine, 4 mg/m2 on Days 1, 8, and 15 (on Day 15 vinblastine was delivered only in the first cycle) (MVC) every 3 weeks for at least 3 cycles. RESULTS: From August 1991 until August 1994, 70 patients entered the trial. All were evaluable for toxicity and response. The median age was 62 years (range, 40-73 years). The male/female ratio was 60:10 (86%:14%); the ratio of Stage III to Stage IV disease was 26:44 (37%:63%); and the ratio of PS > 70 to < or = 70 was 49:21. A total of 296 cycles (median, 4 [range, 1-6 cycles] per patient) were delivered, 280 of 296 (95%) in an outpatient setting with only 4 patients requiring hospitalization for treatment delivery. Overall response rate (RR) was 38.6% (95% confidence interval [CI], 27-51%) (1 complete response, 1.5%; 26 partial responses, 37.1%). Median duration of response was 9.8 months (range, 2-27 months). In Stage III patients the RR was 42% and in Stage IV patients it was 34%. Overall median survival was 9.5 months (95% CI, 6.8-15.3 months). Survival at 1 year was 39% (standard error [SE] 3.6%) and was 11% at 2 years (SE 3.6%). In Stage III patients median survival was 13 months and the 1-year survival rate was 54% (SE 10%); Stage IV patients had a median survival of 7.4 months and a 1-year survival rate of 28% (SE 7%). Delivered dose intensity was: carboplatin, 71%; vinblastine, 60%; and mitomycin C, 77% of the planned dose intensity. The back calculation of carboplatin area under the curve (AUC) with Calvert's formula and with the Cockcroft-Gault glomerular filtration rate estimation, showed a median AUC value of 4 (range, 2-8). Using the more precise Chatelut formula, AUC was again 4 (range, 2-7). Hematologic toxicity was the major side effect; Grades 3 and 4 leukopenia were observed in 34% and 6% of patients, respectively, and Grades 3 and 4 thrombocytopenia in 25% and 4% of patients, respectively. Grade 2 infection occurred in 10% of patients, with only 1 case of sepsis; severe constipation and Grade 2 alopecia occurred in only 1 patient; and no case of higher than Grade 1 nephrotoxicity was observed. No pulmonary toxicity was observed. Compliance with treatment was good with only one patient refusal after the first cycle. CONCLUSIONS: Chemotherapy for advanced NSCLS is still controversial, because effectiveness in terms of RR and symptom control must be weighed against treatment toxicity and costs. From our study it appears that MVC is easy to deliver in an outpatient setting, and has good patient compliance, low toxicity profile, and promising RR and response duration. The substitution of carboplatin for cisplatin in regimens for advanced NSCLC should be considered.

The role of chemotherapy in recurrent malignant gliomas: an overview.

First-line treatment of malignant gliomas invariably includes surgery when feasible, and often adjuvant radiotherapy with or without chemotherapy; at progression or recurrence, the only remaining possibility is chemotherapy. While the role of first-line treatment has been established by many randomized studies, second-line treatment is not as well defined. To analyze the difficulties encountered with cytotoxic drugs in relation to both the blood-brain barrier and drug resistance, we examined the results obtained by single-agent chemotherapy, drug combinations, and biological response modifiers. Our findings confirmed that the nitrosoureas are the most active substances at the time of recurrence; these agents give an approximately 30% global response rate, with about 20 weeks' survival. Although no comparative randomized studies regarding single- versus multiple-agent chemotherapy are available, the latter approach, including nitrosourea, can obtain an up to 40% rate of response, with survival ranging from 30 to 50 weeks. The role of interferons has been very controversial; individually, alpha- and beta-interferons seem to give a 20% response rate, with 20 weeks' survival. To date, they have never been used in combination with cytotoxic drugs, but they may prove synergistic without increasing toxicity. Studies addressing the quality of life of these patients are not available, and it is clear that we need more basic research in this field.

Hybrid MOPP/ABVD and radiotherapy in advanced Hodgkin's disease.

BACKGROUND: In patients with advanced Hodgkin's disease (HD), the alternation of MOPP with ABVD or hybrid MOPP/ABVD are associated with a high CR rate and a high probability of 5-year survival. However, even after effective chemotherapy the risk of nodal relapse is not negligible, and not only in initial bulky site(s) of disease. For this reason, in an attempt to prevent relapses after combination chemotherapy alone, we performed a prospective study to evaluate the efficacy and toxic effects of 6 courses of hybrid MOPP/ABVD followed by radiotherapy (RT) in stages II A bulky, II B, III and also in stage IV with bulky disease of residual after chemotherapy. PATIENTS AND METHODS: From January 1985 to August 1993, 133 patients with HD (128 newly diagnosed, stage II A bulky-IV, 5 in first relapse after RT) were treated according to the following program: 6 courses of the hybrid MOPP/ABVD regimen followed by RT (STNI + spleen in stages II A, II B, III without pelvic lymph node involvement, TNI + spleen in stage III with pelvic lymph node involvement, involved field in stage IV with bulky disease or residual after chemotherapy). The total dose of RT was 4000 cGy to the sites of bulky or residual disease and 2000 cGy to the other sites. RESULTS: After hybrid MOPP/ABVD, 107 of 130 (82.3%) fully evaluable patients were classified as in CR or CR(U). After completion of RT, 108 patients were in CR and 3 were in PR, for an overall response rate of 85%. With a median follow-up duration of 45 months, the actuarial 5-year survival is 76% and the progression-free survival 68.6%. So far, only 14 patients have relapsed (6 within the irradiation field) and the 5-year relapse-free survival is 82.5%. CONCLUSION: Six courses of hybrid MOPP/ABVD followed by RT in stages II A bulky, II B, III and in stage IV with bulky disease or residual after chemotherapy produced a high CR rate with low risk of relapse. However, a longer follow-up is necessary to evaluate the late effects of combined therapy.

Continuous mitoxantrone infusion in pretreated epithelial ovarian cancer.

Mitoxantrone has shown moderate activity in advanced epithelial ovarian cancer following intermittent i.v. administration. Experiments and clinical data suggest that long-term continuous drug infusion may achieve a better therapeutic result with less toxicity. This hypothesis was tested in patients with advanced ovarian cancer who had been pretreated with other agents. Mitoxantrone was infused continuously in 21-day courses beginning every 6 weeks. If severe toxicity did not occur, the infusion rate was increased by 0.1-0.2 mg/m2 per day. The mitoxantrone solution proved to be stable over the 21-day infusion period. For ethical reasons an optimal two-stage design was employed. The trial was interrupted at the end of the first recruitment stage because the target of 3 responses out of 13 patients had not been achieved (only 1 patient had a partial response). Hematologic toxicity was observed in 11 patients, and 2 of them had a catheter occlusion. In conclusion, we found that 21-day of infusion of mitoxantrone apparently has no clinical benefit as compared with bolus administration in patients with advanced ovarian cancer.

Prolonged survival (17 years) in a patient with chronic myelogenous leukemia after therapy for Hodgkin's disease.

A case of secondary chronic myelogenous leukemia after successful therapy for Hodgkin's disease is reported. The patient was diagnosed as having stage IIIA Hodgkin's disease, at the age of 33. He underwent staging laparosplenectomy and was treated with radiotherapy plus chemotherapy. Forty three months after the diagnosis of Hodgkin's disease, a Philadelphia-positive chronic myelogenous leukemia developed. It required periodic chemotherapy and each time a remission, lasting several months (up to 14 months), was obtained. The disease had an unusually prolonged clinical course, and the blast crisis, of lymphoid type, occurred only 17 years later.

Late relapses in Hodgkin's disease: outcome of patients relapsing more than twelve months after primary chemotherapy.

BACKGROUND: Patients with Hodgkin's disease whose initial complete remissions (CR) after primary chemotherapy were longer than 1 year are thought to have better prognoses than patients whose initial remissions were shorter than 1 year. However, only a few studies have analyzed the long-term survival in addition to the results of retreatment in patients relapsing after CR lasting more than 1 year. PATIENTS AND METHODS: We analyzed the data of 40 patients with Hodgkin's disease who were treated in a single institution and whose CR were > 1 year after primary chemotherapy. Therapy at relapse was not standardized: of 36 patients evaluable for response, 29 received second-line chemotherapy and 7 received radiotherapy alone. RESULTS: Sixty-five percent of the patients obtained CR (median duration: 21 months). Sixty-eight percent of the complete responders relapsed again; however, long-lasting third and fourth remissions were observed. All of the 7 patients whose retreatment consisted of radiotherapy alone obtained CR, but only 1 is in continuous CR. The presence of nodular sclerosing histologic subtype, the absence of extranodal involvement and the use of hybrid MOPP/ABVD or ABVD alone as salvage treatment are independently associated with a higher CR rate and a higher probability of 5-year survival. The 5-year survival for all 40 patients is 49%. For the patients obtaining CR, the 5-year survival and the 5-year relapse-free survival are 76% and 25%, respectively. However, the survival curve continues to fall in the succeeding years because of third and fourth relapses and the occurrence of secondary acute leukemia and non-Hodgkin's lymphoma. CONCLUSIONS: A high percentage of patients relapsing more than 12 months after primary chemotherapy can obtain second CR. Even if most of our patients eventually relapse, third and fourth CRs are not uncommon. However, the long-term survival is low and it is further diminished by secondary leukemia and non-Hodgkin's lymphoma.

A combination of mitoxantrone, etoposide and prednisone in elderly patients with non-Hodgkin's lymphoma.

From January 1988 to December 1991, 55 elderly patients (14 pretreated and 41 previously untreated) with non-Hodgkin's lymphoma (NHL) entered a prospective study to evaluate the feasibility of a combination of mitoxantrone (7-9 mg/m2), VP 16-213 (150 mg, 2-hour infusion on day 1, and 200 mg per os on days 3 and 5) and low-dose prednisone (25 mg days 1-5) (MVP regimen), recycling every 21-28 days. The median age was 75 (range 64-93). All but 4 pretreated patients had intermediate- or high-grade lymphomas. Complete remissions were obtained in 22 of 40 (55%) evaluable previously untreated patients, and partial remissions in 10 (2 of these obtained complete remissions after radiotherapy), for an overall response rate of 80%. The median duration of response was 12 months. At 24 months the overall survival was 52% and the relapse-free survival was 31%. Of 14 pretreated patients complete remissions were obtained in 4 (29%) and partial remissions in 3. Granulocytopenia and fever were the most important side effects; two patients contracted bronchopneumonia and one of them died. Other toxicities were mild. We conclude that this combination chemotherapy is effective as first-line and salvage treatment in elderly patients with intermediate- and high-grade NHL, and that it is feasible on an outpatient basis, with manageable toxicity.

Deflazacort and fluoximesterone in advanced, pretreated breast cancer.

A very simple, low dose, orally administered regime (10 to 15 mg of fluoximesterone + 6 mg of deflazacort daily for periods of 1 to several months) resulting in mild-acceptable toxicity (essentially some weight gain) determined subjective improvement in 2/3 of 34 evaluable patients (out of 36 treated) and an objective measurable tumor reduction in 1/3, although most patients had been previously treated with chemotherapy and hormone treatment and proved primarily or secondarily refractory. The receptor status at the beginning of fluoximesterone+deflazacort treatment was not known, except in one negative-receptor patient, who responded to the combination after becoming resistant to tamoxifen (see photo). In some patients the condition of hormone refractoriness would suggest a no-treatment policy, but a trial with this regime is always convenient as it may improve both duration and quality of life.

Carboplatin plus 5-fluorouracil and leucovorin in previously treated patients with metastatic breast cancer.

The commonly reported second-line chemotherapy regimens administered for metastatic breast cancer usually induce few responses, which last no more than 4 to 8 months. We used carboplatin 50 mg/m2 on days 2, 3, and 4 of each course, leucovorin 500 mg/m2 on days 1 through 5 in 30-minute infusions, and 5-fluorouracil (5-FU) 375 mg/m2 intravenous bolus 1 hour after each leucovorin dose to treat 32 patients with metastatic breast cancer. Six patients had previously received treatment with only one cytotoxic chemotherapy regimen, usually CMF (cyclophosphamide/methotrexate/5-FU). Twenty-six patients had received treatment with two or more regimens of chemotherapy previously, and most of them also had received radiotherapy and endocrine manipulations. Fifteen patients had visceral deposits. In cases of excessive or persistent toxicity, single daily doses were not reduced, but the start of the next course was delayed or its duration reduced. Of 26 heavily pretreated patients, 12 responded, primarily those with disease in lymph nodes, skin, breast, and pleura. One patient with liver deposits had a complete remission confirmed at laparoscopy and echogram. Survival was probably prolonged, with a median duration of response of 5 months (range, 3 to 22+), and moderate side effects that did not compromise quality of life during treatment. The probability of response was not related to the type of pretreatment (with or without 5-FU) nor to response to previous treatments.