A phase II study of induction chemotherapy with gemcitabine (G) and cisplatin (P) in locally advanced non-small cell lung cancer: interim analysis.

BACKGROUND: Gemcitabine-cisplatin (GP) combination is one of the most active and well tolerated regimens in advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the activity and toxicity of the GP regimen as a 21-day schedule in patients (pts) with stage IIIAN2-IIIB NSCLC. PATIENTS AND METHODS: From October 1997 to July 2000, 47 pts entered the study: 43 were eligible (40 men and three women); median age was 61 years (range 45-73); ECOG PS 0-1; histology was squamous (20 pts), adenocarcinoma (12 pts), large cell (five pts), and undifferentiated (six pts); stage was IIIAN2 (14 pts, 32.56%), and IIIB (29 pts, 67.44%). Malignant pleural effusion or superior vena cava syndrome was criteria of exclusion. Induction treatment consisted of three cycles of GP (G 1250 mg/m(2) i.v. on days 1 and 8, and P 100 mg/m(2) on day 8 every 3 weeks). Responding and stable pts underwent surgery (S) and/or radiotherapy (RT). RESULTS: Following a minimum of two cycles, 39 pts were evaluable for response and 42 for toxicity. Two pts had complete responses (CR; 5.2%), 24 had partial response (PR; 61.5%), eight had stable disease (SD; 20.5%), and five had progressive disease (PRO; 12.8%). WHO grades 3 and 4 anaemia, neutropenia and thrombocytopenia were observed in two, four and two pts, respectively; non-haematological toxicity was moderate. After induction, stable and responding pts received either RT (18 pts) or S+RT (13 pts). Among the 16 resected pts, a radical complete resection was possible in 13 cases (81.3%), whereas tumour down-staging was observed in nine pts (56.2%). CONCLUSION: GP, as a 3-week neoadjuvant schedule, appears a safe and active regimen.

Cisplatin and gemcitabine in non-small-cell lung cancer.

The nucleoside analogue, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC), producing consistent response rates of 20% and above. Because of its unique mechanism of action and its non-overlapping toxicity with other active agents, gemcitabine is an attractive candidate for trials in combination with other cytotoxic agents. In preclinical models, the cisplatin-gemcitabine combination suggested synergy between the two drugs. In phase I-II studies, response rates are as high as 54% when gemcitabine is combined with cisplatin, both in stage III and IV NSCLC. The gemcitabine-containing regimens showed a favourable safety-efficacy profile and compared well with standard regimens used in NSCLC. These preliminary results must be validated by large randomised trials comparing gemcitabine-containing regimens with NSCLC reference chemotherapy regimens.

Mitomycin C, cisplatin, and 5-fluorouracil for advanced and/or recurrent head and neck squamous cell carcinomas.

The combination of cisplatin (CDDP 100 mg/m2 on day 1) and 5-fluorouracil (5-FU 1,000 mg/m2 continuous intravenous (i.v.) infusion days 1-5) is the most widely used chemotherapy regimen for the treatment of advanced head and neck carcinomas, with a response rate of 70-90% but with a survival and a duration of response which are not impressive. Most patients relapse in < or = 2 years and die of cancer. We evaluated the activity of a CDDP (90 mg/m2 on day 1), 5-FU (900 mg/m2/120 h continuous i.v. infusion from day 1), and mitomycin C (MMC 6 mg/m2 on day 1) regimen in advanced or recurrent head and neck squamous cell carcinoma (HNSCC). Fifty-six patients were treated and evaluated for response and toxicity: 5 (9%) complete responses (CR) and 36 (64%) partial responses, (PR) were observed (response rate 73%). The median duration of response was 12 months, and median survival was 15 months. At a median follow-up of 14 months, the estimated overall survival at 1 year was 65%; at 2 years, it was 35%. Grade 3-4 toxicity was noted in 14 patients, mostly hematologic; overall toxicity required a dose-intensity decrease in 20.2% of all cycles. No treatment-related deaths occurred. The regimen showed a good response rate and an encouraging median duration of response with a good tolerability profile.

Cisplatin and etoposide versus cyclophosphamide, epirubicin and vincristine in small cell lung cancer: a randomised study.

From September 1986 until December 1991, 139 patients with histologically-proven small cell lung cancer, age < 75 years, performance status > 40, absence of brain metastases and no previous treatment, were randomised to receive either CEV cyclophosphamide 1000 mg/m2 intravenous (i.v.), epirubicin 70 mg/m2 i.v., vincristine 1.2 mg/m2 i.v., every 3 weeks or PE (cisplatin 20 mg/m2 i.v. and etoposide 75 mg/m2 i.v. for 5 consecutive days, every 3 weeks) for six cycles. After three cycles, responding patients received radiotherapy to the chest (45 Gy/15 sessions) and to the brain (30 Gy/10 sessions--only in patients with limited disease achieving complete remission). 3 patients were ineligible. Patient characteristics included (CEV/PE) total number 66/70, median age 60/61 years, median performance status 80/80, extended disease 33/48 cases (P = 0.04). In evaluable patients, 42/62 (67.7%) responded to CEV while 42/58 (72.4%) responded to PE (P = non-significant); respective complete response rates were 16.1 and 29.3% (P = non-significant) and respective complete response rates in patients with extended disease were 9.4 and 28.9% (P = 0.03). Median survival was 10.5 months, without significant differences in the two treatment arms, even after adjustment for stage. PE was less well tolerated than CEV. Although PE is more active than CEV in certain subsets of patients, its apparent inability to improve survival in this and in other studies questions its routine use in small cell lung cancer.

Reduced lymphocyte subpopulations in patients with advanced or disseminated melanoma.

BACKGROUND: Studies have revealed many features of lymphocyte behavior in patients with malignant melanoma, but there are conflicting results. OBJECTIVE: The aim of this study was to measure with easily reproducible assays the circulating lymphocytes and other immunologic aspects in 33 patients with advanced or disseminated malignant melanoma (MM). METHODS: The following variables were measured: circulating monocytes; total lymphocytes; B (CD19) and T-cell subpopulations; CD3, CD4, and CD8, natural killer cells (anti-Leu-7+ or CD57 and anti-Leu-11+ or CD16) (cytofluorimetry); plasma levels of IgG, IgA, IgM, and IgE; complement fractions 3, 4, and 1Q; antibodies against foreign microorganisms (AaM) (adeno, herpes simplex, herpes zoster, measles, parotitis, cytomegalo, Epstein-Barr, and rubella viruses) and Toxoplasma; and cutaneous delayed hypersensitivity (CDH) to recall antigens (tetanus, diphtheria, Streptococcus, tuberculin, Proteus, Trichophyton, and Candida). We also studied 96 healthy persons, matched for age and geographic location, who were tested on the same days as the patients. RESULTS: In MM the number of total lymphocytes and subsets CD19, CD3, CD4, and CD8 was decreased from 25% to 40% (p < 0.001). The CD4/CD8 ratio increased (22%, p < 0.005) because of the relatively greater decrease of CD8. The CD57 and CD16 cells (expression of natural killer lymphocytes) were consistently reduced (30%; p < 0.002 to p < 0.003). C3 serum level was increased (30%; p < 0.001). Immunoglobulins, CDH, AaM, and all other tests were the same in the two groups. CONCLUSION: The single most important result seems to be a reduction of CD57 and CD16 cells in patients with advanced MM.

Evaluation of the circulating glycoprotein CA549 in mammary cancer and other malignancies.

A prospective study was carried out on a recent marker for breast cancer, CA549, a mucine-like acid glycoprotein present in the fat membranes of human milk. Fifty healthy control subjects and 91 with benign conditions, 103 mammary cancer patients and 256 patients with other types of malignancy were studied. For comparison, CEA and CA15-3 were also investigated. The CA549 cutoff was 11 U/ml. In breast cancer the marker was below the cutoff in 9 cases (92.8%); in malignancies other than breast cancer it was above the cutoff in 5 to 50% of patients. In breast cancer it was raised in 83.3% of cases (CA15-3 showed 82.9% and CEA 50%). In breast cancer after radical surgery, CA549 was normal in patients who were in TNM stage I but above the cutoff in 57.1% of those at more advanced stages. The follow-up study is ongoing among these patients. In all the study conditions, CA549 favorably compared to CA15-3 values, with sensitivity and specificity greater than CEA.

Effectiveness and toxicity of "BELD" polychemotherapy in advanced malignant melanoma.

From January 1985 to December 1987, 17 patients with advanced malignant melanoma were treated with the polychemotherapy regimen BELD (bleomycin, 15 mg subcutaneously on day 1 and 4, vindesine 3 mg/m2 intravenously on day 1 and 5, CCNU 80 mg/m2 orally on day 1 and DTIC 200 mg/m2 intravenously on day 1 through 5) proposed as effective (CR + PR 45%) and tolerable. All patients were evaluable for toxicity and 14/17 also for response after 2 BELD cycles (total n. of cycles was 54). Criteria for response were just the same as those used by Young et al. A complete remission and a partial remission (2/14) have been observed at lymph nodal level, the unique sites of the disease in these two patients. Remission lasted 6 and 4 months, respectively. Two other patients showed a minimal response of 2 and 3 months duration (lymphonodal and cutis, respectively); 9 patients had stabilized disease of 5 months median duration. One case of progression of disease was observed. However, toxicity was relevant because of 2 early deaths after the first cycle, most probably therapy related, nausea and vomiting (82%), leukopenia (17%) and muscle rigors (11%).

A phase II study of mitoxantrone.

Thirty pretreated patients with progressive and measurable solid tumors (24/30 patients) or myeloproliferative diseases (6/30 patients) were given mitoxantrone at the dose of 5 mg/m2/day in 250 ml normal saline over 30 minutes infusion for 3 consecutive days every 3 weeks. A total of 104 cycles were administered, median 3 for each patient. 39/104 cycles were delayed for a median of 9 days (from 2 to 59 days) because of myelodepression grade I to III (median I); no infection or bleeding was observed. Grade I to II alopecia was recorded in 16 patients. Chronic cardiac toxicity was observed in one patient previously treated with adriamycin. Mitoxantrone at the studied dose schedule in heavily pretreated subjects was well tolerated every 3 to 4 weeks. In 25/30 patients evaluable for response, one patient had a PR, another had 25% reduction (both patients previously treated) and eleven patients obtained disease stability. This effectiveness, 1 PR, 1 MR, 11 disease stability, is not negligible when it is considered that mitoxantrone was the seventh median line of therapy and the fifth median antiblastic drug.

[Cyclophosphamide, adriamycin and platinum (CAP) in the preoperative neoadjuvant phase and the therapy phase]. / Ciclofosfamide, adriamicina e platino (CAP) in fase neoadiuvante preoperatoria e in fase curativa.

Forty-two patients with metastasized, and 7 patients with locally advanced forms of carcinoma of the breast were treated with a combination of three drugs: CTX 200-400 mg/sq.m. on days 1, 3 and 5, ADM 40 mg/sq.m. on day 1, and DDP 30 mg/sq.m. on days 1, 3 and 5 (CAP), every 21 days. The 42 patients with metastasized carcinoma had already received substantial pre-treatment by surgery and with adjuvant polychemotherapy +/- chemotherapy on recurrence +/- hormonotherapy +/- radiotherapy. The disease sites were: bone (30%), skin (19%), lymph nodes (13.5%), pleura (12.5%), lung (12%) and liver (11%). The 7 patients with locally advanced carcinoma had not been pre-treated; they received the same chemotherapy in the pre-operative neo-adjuvant phase. Positive responses to CAP in the cases with metastasized carcinoma according to individual disease sites (37 pre-treated patients assessable after at least two courses of therapy) were as follows in percentage terms: 24% bone lesions, 56% skin lesions, 77% lymph node lesions, 30% liver lesions, 56% lung lesions, 22% pleural lesions. 3/37 patients (8%) showed complete remission in all disease sites, while 6/37 showed partial remission. This percentage (8 + 16 = 24%) is encouraging, as CAP, in these patients, represents on average the 3rd to 4th line of therapy. Responses to neo-adjuvant CAP therapy (7 patients assessable after at least two courses of therapy) were as follows: 5 patients showed partial remission after 3-6 courses, 1 complete remission, and 1 objective improvement.(ABSTRACT TRUNCATED AT 250 WORDS)