Massimo Rinaldi

Etoposide versus etoposide plus high‐dose cisplatin in the management of advanced non‐small cell lung cancer: Results of a prospective randomized fonicap trial

Two hundred sixteen patients with unresectable non‐small cell lung carcinoma were randomly allocated to receive etoposide (120 mg/m2, days 1–3) either alone or in combination with high‐dose cisplatin (60 mg/m2, days 1–2). The patients distribution and characteristics were similar in the two treatment arms. The objective response rate for etoposide was 7% versus 25.8% for etoposide plus cisplatin (P < 0.005). Median progression‐free survival in etoposide arm was 3.5 months versus 5 months in the combination arm (P = 0.43). The median survival time for etoposide was 6 months compared with 8 months for etoposide combined with cisplatin (P = 0.87). Significantly more nausea/vomiting (P < 0.005), serum creatinine elevation (P < 0.005), hearing loss and/or tinnitus (P < 0.005), peripheral neuropathy (P < 0.005), leukopenia (P < 0.025), and anemia (P < 0.005) occurred in the etoposide plus cisplatin arm. No statistically significant difference was recorded between the two arms in terms of performance status changes. in conclusion the addition of high‐dose cisplatin to single‐agent etoposide significantly increases the chance of obtaining tumor response in advanced non‐small cell lung cancer at the cost of an increased toxicity without any significant long‐term impact on survival and progression‐free survival.

Treatment of malignant pleural effusions with intracavitary Corynebacterium parvum

Fifty‐three cases of metastatic pleural effusion (30 haemorragic and 23 serofibrinous) were treated with 4 mg of Corynebacterium parvum (CP) injected weekly into the pleural cavity after total thoracentesis. Of the 53 effusions, 24 were metastases from lung cancer and 29 from breast cancer. Complete response (CR) was assessed as total resolution of pleural effusion after explorative thoracentesis. The results were as follows: 15 CR after two injections of CP, 30 CR after three, and 5 CR after the fourth administration. Three of 53 cases could not be evaluated because of early death. Of the 30 clearly haemorragic effusions, 25 turned into serofibrinosis after the first intrapleural injection of CP and the other five after the second. These findings indicate that intracavitary CP is the most adequate treatment for the control of neoplastic pleural effusion because it induces a significant clinical improvement with milder side effects with respect to other drugs and/or physical agents commonly used.

Use of selected combinations of monoclonal antibodies to tumor associated antigens in the diagnosis of neoplastic effusions of unknown origin

While conventional cytodiagnosis can, in most instances, recognize cancer cells in metastatic effusions from solid tumors, the cellular type or the organ of origin of the primary neoplasia can rarely be determined only on the basis of their morphology. In the present study we have evaluated whether immunocytochemical techniques can be used to overcome this limitation by employing a panel of monoclonal antibodies (MoAbs) to tumor associated antigens (TAA) which lack detectable reactivity with mesothelial cells. To this end we have analyzed, by indirect immunofluorescence, cytospins of 60 malignant effusions of unknown origin. The results of this study have shown that the definition of the origin of the primary tumor, which was subsequently confirmed histologically and/or clinically, could be reached in 87% of the cases. These findings demonstrate that selected combinations of MoAbs, when used in immunocytochemical tests, can provide a powerful diagnostic tool in defining the site of cryptic primary neoplasias causing metastatic effusions.

Ambamustine in the second-line treatment of patients with small-cell lung cancer: a phase II Fonicap study.

Despite a high probability of response to first-line chemotherapy, most patients with small-cell lung cancer (SCLC) will eventually have progression of their disease because of the development of resistant disease. Second-line testing of new drugs is an accepted research strategy in SCLC. In this context, the Italian Lung Cancer Task Force (FONICAP) has tested a new synthetic bifunctional alkylating agent, Ambamustine, with preliminary evidence of activity in other solid tumors. Patients with measurable SCLC, progressive after one first-line chemotherapy regimen (either sensitive or refractory), were eligible for the study. Ambamustine was administered at the dose of 2 mg/kg as a 1-hour intravenous infusion on day 1 every 21 days. The dose was to be increased to 3 mg/kg if no grade IV toxicity and complete hematologic recovery had occurred by day 22. Sample size was calculated according to a two-stage optimal Simons design. Seventeen patients were entered into the study. Twelve patients were refractory to prior chemotherapy; 12 had extensive disease; the median age was 64 years (range: 46-75 years) and the median performance status was 1. Among 13 patients who received more than one cycle, 9 patients could increase Ambamustine dose from 2 to 3 mg/kg. No objective response was observed: one patient obtained a 50% regression of the primary tumor with contemporary disease progression in the liver and was qualified as having progressive disease. The treatment was well tolerated: grade IV leukopenia occurred in only 1 patient; grade III anemia occurred in 17.6%, grade III leukopenia in 11.8%, and grade III thrombocytopenia in 23.5%. Nonhematologic toxicity was minimal. Ambamustine, at the dose and schedule used in this study, is well tolerated in pretreated patients with SCLC but has no significant antitumor activity in this unfavorable group of patients.

Combinations of monoclonal antibodies can distinguish primary lung tumors from metastatic lung tumors sampled by fine needle aspiration biopsy

Transthoracic fine needle aspiration (FNA) biopsies performed under computed tomography (CT) scan (CT‐FNA) have greatly improved the cytodiagnosis of lung tumors. However, the distinction between a primary lesion and a metastatic lesion still may be difficult on the basis of morphologic criteria. To evaluate whether a selected panel of monoclonal antibodies (MoAb) to tumor‐associated antigens (TAA) can improve the diagnostic potential of FNA, we have immunocytochemically analyzed 122 pulmonary CT‐FNA. Whereas conventional cytology was capable of recognizing only the neoplastic nature of the lesions, the immunocytochemical diagnosis could identify the primary or metastatic nature of the pulmonary masses in 92.5% of the cases. The immunocytochemical findings were confirmed by clinical—histopathologic data. The current results demonstrate that the use of immunocytochemical methods can significantly improve the diagnostic accuracy of conventional cytology of lung masses. Cancer 64:2493–2500, 1989.

Role of Percutaneous Fine Needle Aspiration in the Diagnosis of Lung Cancer: Our Experience with 140 Patients

The authors have performed percutaneous fine needle aspiration (FNA) biopsy in 140 patients with pulmonary lesions of suspected neoplastic nature. In 63% of the cases histologic diagnosis could be made on the bioptic sample. Comparison of these findings with those obtained with conventional exfoliative cytology suggest that the latter technique gives higher percentage of histological characterization, it is free of complications and easier to perform. Thus, FNA appears to be an additional, irreplaceable tool when conventional methods fail to provide clear-cut information regarding the histologic nature of pulmonary lesions.

Morphological Damage Induced in vivo by Lonidamine on Human Metastatic Cancer Cells

Lonidamine was given to several patients affected with different types of neoplasias growing as metastases both in ascites and pleural effusion, and solid cutaneous metastases. The patients with tumor cells in ascites and pleural effusion were treated with Lonidamine per os or in loco injections. In cutaneous metastases, Lonidamine was administered by different routes: (1) per os; (2) local endoarterial; and (3) in association with hyperthermic perfusion with or without antiblastic drugs.

Improvement of Immunocytochemical Diagnosis of Neoplastic Effusions by Short-Term Culture of the Fluid: A Case Report

The metastatic nature of effusions from solid tumors may remain undetected in about 20% of instances when they are analyzed by conventional cytological techniques [5]. Such failures are mostly due to the scarcity of tumor cells, which may be masked by mesothelial and lymphoid elements. We have recently shown that immunocytochemical methods employing monoclonal antibodies (MAb) to tumor-associated antigens (TAAs) can greatly improve the accuracy of cytodiagnosis of metastatic effusions [7].

Immunocytochemical Diagnosis of Neoplastic Effusions of Unknown Origin Employing Selected Combinations of Monoclonal Antibodies to Tumor-Associated Antigens

Malignant cells in metastatic effusions from solid tumors can easily be detected because of their morphologic features, but their histological type can rarely be defined [4]. The recent availability of an increasing number of monoclonal antibodies (MAbs) to tumor-associated antigens (TAA) may offer a powerful diagnostic complement to conventional morphologic diagnosis for the identification of the organ of origin of the primary tumor. In the present study we evaluated whether the use of selected combinations of MAbs to TAAs which lack detectable reactivity with mesothelial cells may provide useful information in the cytodiagnosis of effusions in patients with unknown primary malignancy. The results of this study show that a panel of selected MAbs is a valuable adjunct to routine cytopathology since it enables identification of the site of primary tumors in 87% of the cases studied.

Fine-Needle Aspirates of Nonpalpable Tumor Masses Guided by Computerized Tomography: Definition of Their Primary or Metastatic Nature Using Immunocytochemical Methods

Fine-needle aspiration biopsies sampled under computerized tomography (CTFNA) is increasingly performed for the cytodiagnosis of nonpalpable tumor masses [5]. While the neoplastic nature of the lesions can be recognized in most instances by morphologic criteria, whether the neoplasia is primary or metastatic can rarely be established. The use of monoclonal antibodies (MoAbs) to tumor-associated antigens (TAAs) in this context has resulted only in a limited improvement because most of the TAAs recognized are not strictly tumor specific and are endowed with variable degrees of heterogeneous expression [12]. In the present study, we have explored whether, instead of this, the use of combinations of MoAbs, selected on the basis of an extensive immunohistochemical testing, may be of potential value for: (a) the diagnosis of primary cancer, and (b) the differentiation between a primary or metastatic lesion. The data presented in this chapter demonstrate that this methodologic approach can significantly improve the cytodiagnosis of CT-FNAs of nonpalpable tumor masses with an accuracy of 84%.