The impact of a psychological intervention on quality of life in non-metastatic breast cancer.

The aim of this study was to determine whether psychological intervention had a beneficial effect on the quality of life and behaviour of women diagnosed with breast cancer. 36 consecutive patients with non-metastatic breast cancer assigned to surgery and systemic chemotherapy were randomised to receive either psychological intervention (weekly cognitive individual psychotherapy and bimonthly family counselling) or standard follow-up. Personality (16-PF and IIQ), quality of life (FLIC), and depression (BDI) scores were the endpoints for this study, and the questionnaires were completed by the patients at diagnosis, and up to 9 months after diagnosis. Cognitive psychotherapy and family counselling improved both depression and quality of life indexes compared with the control group. Better emotional coping behaviours were also revealed by some changes in personality traits in the intervention group.

Carboplatin monochemotherapy in elderly patients with nonoperable transitional cell carcinoma of the bladder: a two-stage, phase II study.

Elderly patients with nonoperable transitional cell carcinoma of the bladder need a rather active, but less toxic treatment than full-dose polychemotherapy. This study was designed to determine whether the cisplatin-analogue carboplatin (which is less nephrotoxic and less neurotoxic than the parent compound) has sufficient activity against T2-T4 neoplasms (both nonmetastatic and metastatic) to warrant further development in phase III trials. Carboplatin dose was adjusted according to creatinine clearance, with a maximum dose of 300 mg/m2. The patient selection for this screening for activity was adjusted by the use of the 'optimal' two-stage design. Seventeen patients were enrolled, with a median age of 78 years (range: 70-85), a median performance status of 80% (range: 70-90%); 13 patients were lymph node-negative (10 T2, 2 T3, 1 T4) and 4 had locoregional or distant node metastases. Nine patients had a complete response (3 in the first, 9-patient, stage, and 6 in the second, 8-patient, stage), demonstrating that carboplatin had sufficient activity (at the 'desirable' target level of 35%); almost all responses were observed in T2 patients. Six patients had stable disease, and 2 had disease progression during treatment. The toxicity was acceptable, with only 41% of patients having grade II-III hematologic toxicity. More than 30% of patients were estimated to be free from progressive disease (54% alive) at 24 months. In our opinion carboplatin is suitable to be tested-in a phase III testing versus full-dose radiation therapy-as adjuvant after initial transurethral resection of the prostate in elderly patients with T2 transitional cell carcinoma of the bladder considered radically nonoperable for medical problems.

A pilot study of concomitant radiation and chemotherapy in patients with locally advanced head and neck cancer.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

The combination of mitomycin, vinblastine and cisplatin is active in the palliation of stage IIIB-IV non-small-cell lung cancer.

Twenty-eight patients with stage IIIB-IV non-small-cell lung cancer were treated with mitomycin C, vinblastine and cisplatin (MVP) in a phase II--minimax 2-stage design--randomized trial (with cisplatin plus etoposide as control arm). As indicated by the study design, the accrual was stopped after the 11th responder, and the combination was considered as active at the 40% level. Forty-six percent of patients had an improvement of their initial Karnofsky performance score, lasting a median of 24 weeks, and about 38% had a complete relief of symptoms. Hematologic toxicity was moderate to severe in about 50% of patients, and neurologic toxicity in about 18%; no grade 4 toxicity was observed. The estimated median progression-free survival was of 25 weeks. The observed activity and manageability, together with the positive effect on patient quality of life, account for a positive evaluation of MVP as a palliative treatment in advanced non-small-cell lung cancer.

Epirubicin, methotrexate and bleomycin in the management of recurrent squamous cell head and neck cancer. A GSTTC randomised phase II study.

53 patients with squamous cell carcinoma of the head and neck recurrent after initial treatment were entered into a phase II trial of the epirubicin, methotrexate and bleomycin (EMB) combination. The primary objective of the study was to evaluate the activity of this combination. Compliance to EMB and the possible non-cross-resistance to previous cisplatin-containing chemotherapy were secondary objectives. In order to avoid patient selection bias, the study involved randomisation between EMB and a cisplatin-methotrexate-bleomycin (DMB) combination (with EMB: DMB = 2:1). 23 out of 53 (43% +/- 13) EMB patients showed an objective response, lasting a median of 12 (range 4-39) weeks; interestingly, 5 out of 14 (36% +/- 25) patients pretreated with cisplatin plus 5-fluorouracil responded to EMB. The treatment compliance was good and a median of three courses was delivered. No patient refused the treatment after the initial cycle. Leukopenia (47%) and oral mucositis (42%) were the main side effects. DMB produced a response rate of 33% +/- 18 with a median duration of 5 (4-13) weeks. None of the patients previously treated with cisplatin plus 5-fluorouracil responded. 5 patients refused the treatment after the first cycle and a median of two cycles (0-5) was delivered. In conclusion, EMB produced results similar to cisplatin-containing regimens, with a mild to moderate toxicity and a good compliance; the possible non cross-resistance with cisplatin plus 5-fluorouracil deserves further evaluation.

Response and toxicity of cisplatin and 120-h 5-fluorouracil infusion in pretreated and untreated patients with advanced epidermoid cancer of the head and neck.

Eighty-two patients with advanced or recurrent squamous cell carcinoma of the head and neck were treated with bolus cisplatin and 120-h infusion of 5-fluorouracil. Among 49 pretreated patients, there were 9 complete and 12 partial responses, for an overall response rate of 43% and a median estimated survival of 8 months. Hematologic toxicity in this group was relevant, with 4 early deaths and 30% of cases with moderate to severe leukopenia; mucosal and renal toxicities were also important. Among 33 patients with no prior therapy, there were 8 complete and 17 partial responses, for an overall response rate of 76%. Fifteen of the 25 responding patients received subsequent locoregional treatment. The median estimated survival in this group was 29 months. Hematologic, mucosal, and renal toxicities were only mild to moderate. Episodes of possible 5-fluorouracil-related cardiotoxicity were recorded in both pretreated and untreated patients. Twelve of 41 partial responses observed after the second cycle of therapy were converted to complete responses with a third (8 cases) and also a fourth (4 cases) course. This study confirmed that cisplatin plus 5-fluorouracil is a first-choice combination in previously untreated patients. Definitive evidence that chemotherapy can favorable influence survival awaits confirmation by randomized trials, using a control arm with conventional locoregional treatment. In previously treated patients with recurrent disease, less intensive regimens not requiring hospitalization seem more useful for the quality of life.

Peptichemio in pretreated patients with plasmacell neoplasms.

Twenty-one patients with alkylator-resistant plasmacell neoplasms were treated with Peptichemio (PTC) at a dose of 40 mg/m2 for 3 days every 3 weeks or, in the case of persistent leukopenia and/or thrombocytopenia, at the single dose of 70 mg/m2 every 2-3 weeks according to haematological recovery. Seventeen patients, 10 with multiple myeloma and seven with extramedullary plasmacytoma (EMP), were fully evaluable. Six of 17 patients (35%) responded: three of seven EMP patients had a complete remission and 3 of 10 multiple myeloma patients had an objective response greater than 50%. The median duration of response was 8.5 months. An EMP patient obtained a complete response lasting for 16 months. The most frequent toxic effect were phlebosclerosis, occurring in all the patients, and myelosuppression, which was severe in only one case. PTC appears to be an active drug in patients with plasmacell neoplasms even if resistant to alkylating agents.

Cis-dichlorodiammineplatinum (II), VP 16-213, and prednisone (DVP regimen) in the treatment of pretreated advanced malignant lymphomas.

Eighteen evaluable patients with advanced malignant lymphoma were treated with a combination of cis-dichlorodiammineplatinum (II) (50 mg/m2 i.v. on day 1), VP 16-213 (100 mg/m2 i.v. on days 1, 3, 5), and prednisone (50 mg/m2 per os on days 1-5), recycling every 2 weeks. All patients were previously pretreated. There were 3 complete remissions (patients with Hodgkin's disease), and 4 partial remission (2 patients with Hodgkin's and 2 with non-Hodgkin's lymphoma), for a median duration of 8 weeks. In addition, 2 minor responses (patients with Hodgkin's disease) were observed. Vomiting and myelosuppression were the most prominent toxic effects. In most heavily pretreated patients, myelosuppression was moderate to severe: in these patients and in patients with bone marrow involvement, a schedule interval of 3 weeks should be more appropriate. Nephrotoxicity was minimal. This combination chemotherapy showed some activity in the management of advanced malignant lymphomas; further studies in this area are justified.

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.

Phase II evaluation of vindesine in mycosis fungoides, extraosseous plasmacytoma and other hematologic malignancies.

We conducted a phase II trial of Vindesine in 24 patients, mostly pretreated (23/24 fully evaluable for therapeutic response) with advanced hematologic malignancies. The drug was administered at weekly bolus doses of 3 mg/m2 i.v. Overall, objective tumor regressions were seen in 9 of 23 patients. The drug appeared effective in extraosseous plasmacytoma (1 complete response, 1 partial response and 1 minor response in 6 patients). Further phase II trials in these 2 diseases are justified. In addition, 3 partial responses in 7 patients with advanced lymphoma were also obtained. Previous vinca-alkaloid exposure did not adversely affect the response rate: 8 of 9 responsive patients had previously received vincristine and/or vinblastine. Drug-related toxic effects were mainly represented by manageable and reversible neurotoxicity and by moderate leukopenia with apparent lack of thrombocytopenia. In heavily pretreated patients, leukopenia may be occasionally severe: in these conditions a starting dose of 2 mg/m2 seems more appropriate.

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.