Chemotherapy of breast cancer in the elderly.

Breast cancer arises in about 48% of patients older than 65 years and more than 30% occurs in those over 70 years being the leading cause of cancer-related death in women older than 65. Elderly patients tolerate chemotherapy poorly compared to their younger counterpart because of progressive reduction of organ function and comorbidities related to age. For this reason, the elderly have been excluded from or underrepresented in most cancer studies and, in clinical practice, they often receive inadequate and untested treatments. For adjuvant chemotherapy, a low percentage of patients over 70 years of age were included in few trials and always in a proportion much lower than the prevalence of cancer in that age group. Adjuvant chemotherapy, preferably including an anthracycline especially in patients with HER-2/neu-positive tumours, seems to be beneficial in older women who have substantial risk of dying of breast cancer. To date even if there is no specifically randomised study, single-agent chemotherapy probably might be considered a reasonable treatment for advanced breast cancer in the elderly. One of the actual main field of clinical research in the treatment of breast cancer is the role of targeted therapies. Chronologic age is a risk factor for toxicities such as myelosuppression and mucositis, and older patients may require more supportive care. In order to plan medical treatment in breast cancer elderly patients is mandatory to practice a comprehensive geriatric assessment that includes evaluation of comorbidities, functional dependence, socio-economic, emotional and cognitive conditions, an estimate of life expectancy and recognition of frailty. The authors review the literature regarding age-specific chemotherapeutic issues in the management of breast cancer elderly patients.

Selective cyclooxygenase-2 inhibitors and non-small cell lung cancer.

Lung cancer is the leading cause of death from cancer in most developed nations. The most common type of lung cancer is of non-small cell histology, representing approximately 80% of the total. Despite aggressive treatments in early stages and improvement of polychemotherapy outcomes in advanced disease, the five years survival rate for lung cancer remains under 15%. Fortunately, our improved knowledge of tumor biology and mechanisms of oncogenesis suggests several new potential targets for clinical research in cancer therapy. A substantial body of evidence indicates that cyclooxigenase (COX)-2 and prostaglandins (PGs) play an important role in tumorigenesis. Mechanisms involved in COX-2 participation in tumorigenesis and tumor growth include xenobiotic metabolism, angiogenesis stimulation, inhibition of immune surveillance and inhibition of apoptosis. COX-2 is frequently overexpressed in bronchial premalignancy, lung adenocarcinoma and squamous cell carcinoma and COX-2 overexpression is a marker of poor prognosis in surgically resected stage I non-small cell lung cancer. Treatment with COX-2 inhibitors reduces the growth of NSCLC cells in vitro and in xenograft studies. Recent studies have defined some of the mechanisms involved in COX-2 participation in NSCLC development and diffusion. These evidences support the hypothesis that selective COX-2 inhibitors (coxibs) may prove beneficial in the prevention and treatment of NSCLC.

Phase I study of epirubicin plus vinorelbine with or without G-CSF in advanced non-small cell lung cancer.

The present phase I study was designed to determine the maximum tolerated dose (MTD) of epirubicin, administered every 3 weeks to patients with advanced non-small cell lung cancer (NSCLC), and combined with a conventional dose of vinorelbine [25 mg/m2 intravenously (i.v.) days 1 and 8] with or without the support of granulocyte-colony stimulating factor (G-CSF). 18 patients entered the study. The patients received the following four dose levels of epirubicin (i.v., day 1): 50 mg/m2 (3 patients) and 60 mg/m2 (6 patients) without G-CSF, 75 mg/m2 (3 patients) and 90 mg/m2 (6 patients) with G-CSF (5 micrograms/kg days 4-6 and 9-15). In the patients treated without G-CSF the MTD of epirubicin was 60 mg/m2 and leukopenia was the dose-limiting toxicity. In the patients treated with G-CSF the MTD was 90 mg/m2, myelotoxicity being the dose-limiting toxicity. We observed 1/3 partial response (PR) with epirubicin at the dose of 75 mg/m2 and 2/6 PR at 90 mg/m2. These results would indicate the usefulness of a phase II study with epirubicin at the dose of 90 mg/m2 in association with conventional dose of vinorelbine with the support of G-CSF in advanced NSCLC.

Mitomycin C plus vindesine or cisplatin plus epirubicin in previously treated patients with symptomatic advanced non-small-cell lung cancer.

A total of 40 previously treated patients with symptomatic advanced non-small-cell lung cancer (NSCLC) were subjected to second-line chemotherapy with mitomycin C plus vindesine (MV) or cisplatin plus epirubicin (PE). The 12 patients treated with the MV regimen showed no objective response (OR) or symptom palliation. In the 28 patients who received the PE regimen, we obtained a 25% partial response rate, with amelioration of tumor-related symptoms occurring in 35.7% of cases and improvement in the performance status being noted in 25% of subjects. Both regimens were well tolerated. These data show that the administration of cisplatin-based second-line chemotherapy to patients with symptomatic advanced NSCLC may be useful.

Phase II study of mitomycin C, etoposide and vindesine in metastatic stage IV non-small-cell lung cancer.

A total of 72 patients with metastatic stage IV non-small-cell lung cancer (NSCLC) were treated with combination chemotherapy comprising the MEV regimen (mitomycin C, 8 mg/m2 given i.v. on day 1; etoposide, 100 mg/m2 given i.v. on days 1-3; and vindesine, 3 mg/m2 given i.v. on day 1; treatment repeated every 3 weeks). In 65 evaluable patients, the objective response rate was 37% (complete responses, 4.7%; partial responses, 32.3%). The median survival was 7.6 months for all patients. The treatment was very well tolerated. MEV proved to be an active and non-toxic regimen for the treatment of metastatic NSCLC.

Second-line chemotherapy of advanced colorectal cancer with sequential high-dose methotrexate and 5-fluorouracil.

Twenty-five patients with pretreated advanced colorectal carcinoma were subjected to second-line chemotherapy with sequential high-dose methotrexate and 5-fluorouracil. In 20 evaluable patients 2 (10%) partial responses, 12 (60%) stable disease and 6 (30%) progressions were observed. Partial responses were maintained for 3 and 4 months respectively; stable disease had a median duration of 4 months. The overall median survival after progression was 7 months. From our results sequential high-dose methotrexate and 5-fluorouracil cannot be recommended as second-line chemotherapy in advanced colorectal cancer.

Clinical trial with 5-fluorouracil and leucovorin.

Many clinical trials with 5-fluorouracil and leucovorin have been reported. This combination therapy seems to play an important role in untreated advanced colorectal cancer. In other neoplasms (gastric, head and neck, breast cancer) further studies are required.

Mitomycin C etoposide and vinorelbine (MEV II) in the treatment of metastatic stage IV non small cell lung cancer.

AIMS AND BACKGROUND: In a prior study with a new non-cisplatin-based regimen including mytomycin C, etoposide and vindesine (MEV I) we observed a 37% response rate and very low toxicity in stage IV non small cell lung cancer. In an attempt to improve the activity of MEV I we evaluated a new regimen, MEV II, a modification of MEV I in which vinorelbine replaced vindesine. METHODS: 21 patients with metastatic stage IV non small cell lung cancer entered the phase II trial and were treated with the MEV II regimen (mitomycin C 8 mg/m2, i.v., d 1, etoposide 100 mg/m2, i.v., d 1-3, vinorelbine 30 mg/m2, i.v., d 1, every 4 weeks. RESULTS: We observed a partial response rate of 30% (95% confidence limits 10-50) with a median survival of 6 months. The worst reported toxicity was leukopenia grade 4 in 10% of patients including one who died of sepsis and grade 3 in 20%. CONCLUSIONS: The MEV II regimen showed a similar activity but greater toxicity than MEV I.

Mitomycin C and vindesine: an ineffective combination chemotherapy in the treatment of malignant pleural mesothelioma.

Twelve patients with malignant pleural mesothelioma were subjected to mitomycin C (MMC) and vindesine (VDS) chemotherapy (MMC 10 mg/m2, i.v., d 1; VDS, 3 mg/m2, i.v., d 1-8, every 4 weeks). No objective response was obtained; 3 (25%) patients had stable disease and 9 (75%) progression of disease. We conclude that MMC plus VDS is an ineffective combination chemotherapy in the treatment of malignant pleural mesothelioma.

Complete regression of laryngeal involvement by classic Kaposi's sarcoma with low-dose alpha-2b interferon.

We report the case of an 82-year old Italian female with laryngeal involvement of classic Kaposi's sarcoma. We obtained a complete regression of laryngeal lesion with low-dose alpha-2b interferon.

Salvage chemotherapy with CCNU and methotrexate for small cell lung cancer resistant to CAV/PE alternating chemotherapy.

CCNU and methotrexate were employed as salvage treatment in 34 small cell lung cancer patients resistant to CAV/PE alternating induction chemotherapy. In the 33 evaluable patients we observed an objective response rate of 21.2% and 3% complete response; median survival was 4 months with 2 patients alive 18 months from starting salvages chemotherapy. The treatment was well tolerated. CCNU and methotrexate has shown to be a moderately active and tolerable salvage treatment for small cell lung cancer after CAV/PE alternating first-line chemotherapy.

Partial response of metastatic hepatocellular carcinoma after treatment with thymostimulin.

We describe a case of partial regression of metastatic hepatocellular carcinoma after treatment with thymostimulin. The patient, a 58-year-old man, received no specific therapy for his tumor, but only a thymus extract ("thymostimulin"). At follow-up 6 months later the patient showed clinical improvement, reduction of alpha-fetoprotein level an liver lesions, and a complete regression of lung metastases. The patient died of progression of the disease with 2-year overall survival.

Irradiation of the hypothalamic-hypophyseal area induces complete regression of mucocutaneous lesions in disseminated histiocytosis X.

We report on a 54-year-old woman with disseminated histiocytosis X who had a complete regression of all mucocutaneous lesions within 1 month from the completion of radiation therapy (4500 cGy) to the hypothalamic-hypophyseal (H-H) area. This response lasted 12 months, after which new cutaneous and bone lesions appeared.

Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. The "Gruppo Oncologico Centro-Sud-Isole' (G.O.C.S.I.).

PURPOSE: To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. PATIENTS AND METHODS: 204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/m2+cisplatin 100 mg/m2 i.v. day 1 and vindesine 3 mg/m2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/ m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1 to 3 with cycles repeated every 3 weeks. For both treatments a maximum of 6 cycles was planned. Response and toxicity were evaluated according to WHO. Subjective responses were assessed by numerical scales. Analyses were made on the basis of intent to treat. RESULTS: The objective response rate was 21.4% (1 CR + 21 PR among 103 patients) in the MEV and 28.7% (1 CR + 28 PR among 101 patients) in the MVP arm (P = 0.48). Symptoms were similar in the two arms. 196 patients progressed and 182 died. The median times to progression were 10 weeks (95% CI 9-12) and 12 weeks (95% CI 10-15) and median survivals were 29 weeks (95% CI 25-36) and 28 weeks (95% CI 25-35) in the MEV and MVP arms, respectively. The relative risks of progressing and of dying were 0.89 (95% CL 0.66-1.20) and 0.96 (95% CL 0.71-1.30), respectively, for patients receiving MVP as compared with those receiving MEV at multivariate analysis adjusted by sex, age, histologic type, number of metastatic sites, performance status at entry, and centre. CONCLUSIONS: In the present study, no significant differences were observed in response rate, survival or palliation of symptoms between the MEV and MVP regimens, while toxicity was significantly more frequent and severe with MVP. Thus, MEV should be considered a reasonable alternative to the MVP regimen in the treatment of stage IV NSCLC.