Long-term survival in a randomized study of nonplatinum therapy versus platinum in advanced epithelial ovarian cancer.

The purpose of this study was to compare long-term survival in first-line chemotherapy with and without platinum in advanced-stage ovarian cancer. From July 1987 to November 1992, 161 untreated patients with FIGO stage III-IV epithelial ovarian cancer were randomized: 81 patients received no platinum and 80 received platinum combination. Residual disease after surgery was <2 cm in 61 patients without platinum, 59 with platinum. Median age was 58 years in nonplatinum arm and 55 years in platinum arm (range: 15-73). Complete and partial responses were 51% and 10% for nonplatinum arm and 51% and 8% for platinum arm, respectively (P= 0.7960). Stable disease was observed in 18% of patients in nonplatinum arm and 15% of patients in platinum arm and progression in 20% of nonplatinum- and 21% of platinum-treated cases. Ten-year disease-free survival was 37% for therapy without platinum and 31% for platinum combination (P= 0.5679); 10-year overall survival was 23% without platinum and 31% with platinum combination (P= 0.2545). Fifteen-year overall survival showed a trend of short duration in favor of platinum (P= 0.0678). Relapses occurred after 60 months in ten patients (seven with and three without platinum). The overall and disease-free survivals at 5, 10, and 15 years show no statistically significant long-term advantage from the addition of cisplatin; however, there is a slight trend in its favor.

Elderly ovarian cancer: treatment with mitoxantrone-carboplatin.

OBJECTIVE: Data concerning optimal treatment of elderly patients with ovarian cancer are scanty. The management of ovarian cancer in the aged patient is many-sided: the diagnosis can be difficult and delayed, and aggressive surgery is often not attempted because of concomitant morbidity. We tested a combination of carboplatin and mitoxantrone potentially associated with low toxicity in elderly patients with ovarian cancer. METHODS: Eighty-two patients older than 70 years (median age, 75; range, 70-88) with epithelial ovarian cancer were referred to our multicenter group and enrolled into this pilot study. Carboplatin (JM8) was given at the dose of 230 mg/m2 and mitoxantrone at the dose of 9 mg/m2 every 28 days. RESULTS: Dose-limiting toxicity was represented by 4 cases of thrombocytopenia and 1 case of gastrointestinal toxicity. These 5 episodes occurred in 328 assessable cycles, representing a low toxicity profile (3%). Of the 68 assessable patients, 36 (53%) did not respond to chemotherapy (no change + progressive disease), complete response was observed in 15 (22%), and partial remission was observed in 16 (23.5%), accounting for an overall response rate of 45%. CONCLUSION: The carboplatin-mitoxantrone combination, at the dosage tested in this study, appears to be well tolerated by elderly patients with advanced ovarian cancer and is associated with an acceptable response rate. Optimally debulked patients also showed improved survival when compared with patients with more extensive tumor.

Gastric non-Hodgkin's lymphoma: analysis of 252 patients from a multicenter study.

AIMS AND BACKGROUND: The stomach is the most common site of primary extranodal non-Hodgkin's lymphoma (NHL) and no agreement has been reached so far on the best therapeutic approach. The main objects of this study were to report the long-term results and to evaluate the importance of some possible prognostic factors in a large series of patients. NHL was considered primary gastric if the main symptoms at presentation were those of gastric disease. METHODS AND STUDY DESIGN: We analyzed 252 consecutive patients treated between 1980 and 1993 in five hospitals in north-east Italy. According to the Working Formulation, 98 patients had low grade lymphoma, 59 intermediate grade (D to F), 81 G or high grade and 14 were not classified. The patients were divided into two groups: one including patients with limited disease (localized to the stomach or perigastric lymph nodes: 165 patients) and one including those with advanced disease (87 patients). The treatment consisted of surgery, chemotherapy, radiotherapy or combinations of these. Sixteen patients received only supportive therapy. RESULTS: The five-year overall survival was 65.4%: 80.3% for patients with limited disease and 36.7% for those with advanced disease (P < 0.0001). Among the limited disease patients the five-year survival was 84.4% for those treated with gastrectomy alone and 88.7% for those who received also adjuvant chemotherapy (P = 0.11). However, while chemotherapy did not improve survival in low grade NHL, it seemed to produce a better survival in the intermediate and high grade groups (P = 0.06). Twelve patients were treated with primary chemotherapy and the five-year survival was 71.2%. In multivariate regression analysis the most important variable for overall survival was surgery for the whole group of 252 patients (P < 0.0001), while it was age for the group with limited disease (P = 0.0008). CONCLUSIONS: Surgery alone can be curative for most patients with gastric lymphoma limited to the stomach or to the perigastric lymph nodes; surgery followed by chemotherapy seems to produce better results than surgery alone in intermediate and high grade lymphomas. Also a non-surgical approach with first-line chemotherapy is associated with a high rate of complete remissions and five-year survival. In advanced disease the five-year survival is similar to that of nodal NHL.

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.

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.

Cisplatin, bleomycin and methotrexate in the treatment of advanced oesophageal cancer.

From February 1981 to September 1982, 34 patients with metastatic or locally advanced (inoperable) epidermoid carcinoma of the oesophagus were treated with a combination of cisplatin, bleomycin and methotrexate. Thirty-one patients are now evaluable for response: 16 of 31 (52%) experienced some improvement, but only eight (26%) obtained major responses (one complete and seven partial). Responses were obtained rapidly within the first two courses. The median duration of responses was 5 months. The median survival from start of therapy was 8 months for responsive and 5 months for non-responsive patients. Gastrointestinal toxicity (cisplatin-related) and mild myelosuppression were the most prominent side-effects. This combination chemotherapy proved to be only of small efficacy in the long-term control of advanced oesophageal cancer. However, because the responses were obtained rapidly, it is conceivable that a similar regimen (with increased dosage of cisplatin) applied before surgery to patients with limited disease could obtain a reduction of the bulky tumour, with a possible increase of the resectability rate and destruction of micrometastases.

Serum lactate dehydrogenase (LDH) as a prognostic index for non-Hodgkin's lymphoma.

According to pretreatment values of serum lactate dehydrogenase (LDH), 113 consecutive patients with non-Hodgkin's lymphoma were divided into three levels: level 1 (within normal range) with LDH less than 250 U/l; level 2 (moderately increased) with LDH between 250 and 500 U/l; level 3 (highly increased) with LDH more than 500 U/l. LDH was elevated in 46 of 113 patients (41%). Normal values of LDH were associated with a better response to therapy and a longer survival, independent of histological type and clinical stage, with one exception; in stage IV patients conclusions could not be drawn concerning the response to therapy (complete remission occurred only in 8 of 44). Even though level 2 patients behaved slightly better than level 3 patients, no statistical difference has been observed between the two levels. Accordingly, serum LDH can be considered a useful predictor of response to therapy and of survival in non-Hodgkin's lymphoma.

Serum copper level in non-Hodgkin's lymphomas.

Serum copper level (SCL) was studied by the atomic absorption technique in 103 patients with non-Hodgkin's lymphoma. SCL was increased in 61% of patients at diagnosis or during active disease; values within normal range were found in 88% of patients in complete remission. The difference between mean SCL during active disease and in remission was highly significant, independently of stage and histologic type, so that: a) Within the same clinical stage high SCL at diagnosis was associated with poorer response to therapy in stage II and stage III (respectively P = 0.033 and P = 0.049), but not in stage IV, where the complete remissions were only 8 out of 42. A shorter 5-year survival was also shown in stages III and IV with high SCL at diagnosis (respectively P less than 0.025 and P less than 0.05), but not in stage II where the deaths were only 3 out of 24. b) Within histologic types, SCL is a useful prognostic index of response to therapy and survival, although a statistically significant difference was only reached for poorly differentiated lymphocytic lymphoma. We conclude that SCL may be a good parameter of disease activity and a useful index of response to therapy and survival in non-Hodgkin's lymphoma.