Silvio Monfardini

Comprehensive Geriatric Assessment Adds Information to Eastern Cooperative Oncology Group Performance Status in Elderly Cancer Patients: An Italian Group for Geriatric Oncology Study

PURPOSE To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (> or = 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satarianos index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL-independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two-fold higher probability of having an elevated Satarianos index than independent patients. A strong association emerged between PS and CGA, with a nearly five-fold increased probability of having a poor PS (ie, > or = 2) recorded in patients dependent for ADL or IADL. CONCLUSION The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients.

Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP

This paper reports the preliminary results of a controlled study randomizing MOPP vs. a new four‐drug combination (ABVD) in advanced Hodgkins disease. ABVD consists of 6 cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide. The purpose for designing this new combination was two‐fold: to compare the efficacy of ABVD with MOPP, and to demonstrate absence of cross‐resistance between the two regimens. Of 60 patients entered into the study, 45 (MOPP 25, ABVD 20) are presently evaluable for the analysis of remission induction. No patient was previously treated with chemotherapy; 20% had relapsed after primary radiotherapy. Whenever possible, complete remission was defined also through rebiopsy of known organ involvement. Complete remission occurred in 76% of patients treated with MOPP and in 75% of those given ABVD, with no difference between the two regimens as far as stage (IIIB–IIIs and IV), histologic type, and prior irradiation were concerned. Crossover carried out for progressive disease or for relapse after initial remission showed absence of cross‐resistance between MOPP and ABVD. Toxic manifestations after ABVD were in general well tolerated and reversible. The percent of optimal dose for each drug was as follows: adriamycin 87%, vinblastine 87%, bleomycin 96%, and imidazole carboxamide 96%. These preliminary results indicate that in terms of complete remission, ABVD could represent a successful alternative to MOPP to be used either in MOPP failures or in sequential combination with MOPP. However, the lack of long‐term followup limits at the present time an adequate comparison between the two treatments.

RADIOTHERAPY VERSUS RADIOTHERAPY ENHANCED BY CISPLATIN IN STAGE III NON-SMALL CELL LUNG CANCER

Abstract Between January 1987 and June 1991, 173 patients with inoperable non-small cell lung cancer, Stage III, were entered into a randomized trial comparing radiotherapy only (RT) (45 Gy/15 fractions/3 weeks) (arm A) versus RT and a daily low dose of cDDP (6 mg/m 2 ) (arm B). An overall response rate of 58.9% was observed in arm A and 50.6% in arm B, respectively. No differences in the pattern of relapse were noted between the two treatment groups. Median time to progression was 10.6 months for arm A and 14.2 months for arm B. Median survivals were 10.3 months and 9.97 months, respectively. Toxicity was acceptable and no treatment-related death occurred in either treatment schedule. In this study no significant advantage of the combined treatment over radiation therapy only was found. The encouraging results achieved in some trials together with the intractability of the disease suggest that further efforts should be made to optimize clinical trial protocols, perhaps by reviewing the radiobiological and pharmacological basis of the combined treatment.

Improved five year survival after combined radiotherapy-chemotherapy for stage I-II non-hodgkin's lymphoma

Abstract In order to improve the prognosis of patients with localized non-Hodgkins lymphomas (NHL) who are treated with radiotherapy (RT), a prospective controlled study utilizing a combined modality approach was carried out in patients with pathologic Stage 1[-II NHL. After treatment with regional RT, patients in complete remission were randomized to receive either no further therapy or 6 cycles of cyclophosphamide, vincristine and prednisolone (CVP). At 5 years from completion of irradiation, the relapse-free survival was 46.3% after RT and 72.1% after RT plus CVP ( P = 0.005). The corresponding findings for the overall survival calculated from the beginning of irradiation were 55.8 and 82.8% respectively ( P = 0.03). The favorable effects of adjuvant chemotherapy on relapse-free survival were statistically significant only in the subgroup with diffuse histology. In patients who relapsed after RT alone, the salvage therapy failed to induce a high incidence of second durable remission. Adjuvant chemotherapy is indicated to improve the cure rate in pathologic stage I-II NHL with diffuse histology when regional RT is utilized.

Hepatitis C virus and non-Hodgkin's lymphomas

Hepatitis C virus (HCV) seems to be the aetiologic agent of mixed cryoglobulinaemia, and as this ‘benign’ lymphoproliferative disorder can frequently develop into more aggressive haematological disorders, this study was undertaken to determine the prevalence of HCV infection in non‐Hodgkins lymphomas. 199 unselected subjects treated by three haematological centres in Northeast Italy were investigated for the presence of HCV infection. As controls, the prevalence of HCV infection was determined in a group of patients affected by other haematological malignancies (153 subjects) and in the general population of the same geographical area in the cohort study called the Dyonisos project (6917 subjects).

Human immunodeficiency virus-related lymphoma treatment with intensive combination chemotherapy☆

Abstract purpose: An increased risk of high-grade non-Hodgkins lymphoma is observed in patients who are seropositive for human immunodeficiency virus (HIV). Treatment of such patients is complicated by their underlying acquired immunodeficiency syndrome (AIDS). Intensive strategies such as those used in non-HIV-related lymphoma may be poorly tolerated. However, patients without severe AIDS may derive significant benefits from such an approach. In a prospective multicenter study, treatment outcomes were assessed in 141 cases of HIV-seropositive lymphomas submitted to aggressive chemotherapy. patients and methods: Adult patients with lymphoma with a performance status less than 3 and no active opportunistic infection were consecutively treated with three cycles of doxorubicin 75 mg/m2, cyclophosphamide 1,200 mg/m2, vindesine 2 mg/m2 for 2 days, bleomycin 10 mg for 2 days, and prednisolone 60 mg/m2 for 5 days (ACVB). This treatment was followed by a consolidation phase of high-dose methotrexate plus leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH84). Central nervous system prophylaxis with intrathecal methotrexate was routinely used. Zidovudine maintenance therapy was started after chemotherapy. Ninety-three patients had high-grade lymphomas (59 Burkitts type) and 48 had intermediate-grade lymphomas. Disseminated stage III-IV was present in 86 patients, meningeal involvement in 29, and bone marrow infiltration in 30; 62 patients had more than 2 extranodal localizations. Lactate dehydrogenase levels were above the normal value in 95 cases. The median CD4-positive lymphocyte count was 227 X 106/L. results: Eighty-nine patients (63%) achieved complete remission (CR) and 19 (13%) partial remission, whereas 13 did not respond and 20 (14%) died during the course of ACVB, 8 of them from progressive disease. With a median follow-up of 28 months, median survival and disease-free survival were 9 and 16 months, respectively. Median survival for nonresponders was 5 months; 23 patients died of opportunistic infections while in persistent CR. In multivariate analysis, four factors were strongly associated with shorter survival: (1) CD4 count less than 100 × 106/L, (2) performance status greater than 1, (3) immunoblastic lymphoma, and (4) prior AIDS. In the absence of all risk factors, the probability of survival at 2 years was 50%. conclusion: In a selected group of HIV-related lymphomas, intensive chemotherapy with LNH84 is feasible and yields a high CR rate. Survival is short due to death from HIV-related infections; however, in a subgroup of patients without adverse prognostic factors, long-term remission was observed.

Unusual malignant tumours in 49 patients with HIV infection

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposis sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found. Testis carcinoma occurred mainly in patients in an early phase of HIV infection, without adversely affecting full-dose chemotherapy or radiotherapy. In situ cervical carcinoma treated with conization would suggest papanicolaou shear test screening in young IVDA. Lung carcinoma occurred in a young age group with rapid progression and resulted in death within 2 months. Intensive chemotherapy for ALL was not adversely affected by HIV infection and two complete remissions were achieved (11 and 15 months duration). This retrospective study shows that while oral and anorectal tumours were very rarely observed, a wide spectrum of other HIV-related solid tumours and leukaemias were found in this IVDA-based series. The incidence of such tumours is probably underestimated because they are not diagnostic of AIDS. The required therapeutic approaches may not necessarily be influenced by HIV infection, in contrast with the observed pattern for treatment of KS and ML in HIV-infected subjects.

Clinical evaluation of adriamycin, a new antitumour antibiotic.

Adriamycin, a new antitumour antibiotic of the anthracycline group with a structural formula very similar to daunorubicin, has proved to have potent tumour-growth-inhibiting properties, and to be particularly effective in childhood malignancies. Though adriamycin produces a higher percentage of side-effects than daunorubicin—namely, stomatitis and alopecia—a lower dosage may be used for therapy.

Second-Line Chemotherapy With Irinotecan Plus Carmustine in Glioblastoma Recurrent or Progressive After First-Line Temozolomide Chemotherapy: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

PURPOSE Glioblastoma multiforme (GBM), the most frequent brain tumor in adults, is not considered chemosensitive. Nevertheless, there is widespread use of first-line chemotherapy, often with temozolomide, as a therapeutic option in patients with progressive disease after surgery and radiotherapy. However, at the time of second recurrence and/or progression, active and noncross-resistant chemotherapy regimens are required. The aim of the present multicenter phase II trial, therefore, was to ascertain the efficacy of second-line carmustine (BCNU) and irinotecan chemotherapy. PATIENTS AND METHODS Patients with histologically confirmed GBM, recurring or progressing after surgery, standard radiotherapy and a first-line temozolomide-based chemotherapy, were considered eligible. The primary end-point was progression-free survival at 6 months (PFS-6), and secondary end-points included response rate, toxicity, and survival. All patients were on enzyme-inducing antiepileptic prophylaxis. Chemotherapy consisted of BCNU (100 mg/m2 on day 1) plus irinotecan (175 mg/m2/weekly for 4 weeks), every 6 weeks, for a maximum of eight cycles. In the absence of grade 2 toxicity, the irinotecan dose was increased to 200 mg/m2. RESULTS A total of 42 patients (median age, 53.4 years; median Karnofsky performance status, 80; range, 60 to 90) were included in the study. PFS-6 was 30.3% (95% CI, 18.5% to 49.7%). Median time to progression was 17 weeks (95% CI, 11.9 to 23.9). Nine partial responses (21.4%; 95% CI, 9% to 34%) were obtained. Toxicity was manageable. CONCLUSION The BCNU plus irinotecan regimen seems active and non-cross-resistant in patients with GBM with recurrence after temozolomide-based chemotherapy.

Malignant Lymphomas of Waldeyer's Ring: Natural History and Survival after Radiotherapy

The natural history of 292 consecutive cases of reticulum cell sarcoma and lymphosarcoma of Waldeyers ring and the survival rate after radiotherapy are reported. In our institute since 1928 from 30 to 35% of pharyngeal neoplasms have been lymphomas, and of these 55% have been reticulum cell sarcomas, 21% lymphosarcomas, and 1% Hodgkins disease. This high incidence may probably be ascribed to the fact that in all malignant lymphomas, irrespective of the clinical presentation, a systematic biopsy of the whole Waldeyers ring was carried out. Pharyngeal lymphomas were confined to Waldeyers ring in 19·6% of cases, with initial spread to contiguous cervical nodes in 43·8%, to distant nodes in 24·2%, and to extranodal tissues in 12·4%. Lymphography showed abnormal retroperitoneal lymph nodes in 38·3% of cases. There was gastrointestinal involvement either initially or later in 17·6% of cases. High-energy radiation therapy to both sides of the neck was the treatment of choice for local and regional disease. It achieved a five-year survival rate of 41·9% in the group of 97 patients treated during the past decade. The incidence of relapse (recurrence and new manifestations) was highest in the first year after treatment.