Low dose fractionated cisplatin plus gemcitabine for elderly patients with advanced non small cell lung cancer: a retrospective analysis.

The aim of the study was to evaluate safety and efficacy of gemcitabine-cisplatin in elderly patients with advanced non small cell lung cancer (NSCLC). This study included 59 patients aged >70 years consecutively admitted to our Department. treatment consisted of gemcitabine 1000 mg/m(2) on days 1 and 8, and low-dose fractionated cisplatin 20 mg/m(2) on days 1, 2, 3 of a 21-day cycle. Toxicity was graded according to the world Health Organization (WHO) criteria.A total of 281 cycles was administered. Hematological toxicities of grade 3 and 4 were seen in 17% and 5% of patients, respectively. Grade 3 gastrointestinal toxicity was 3%, grade 2 neuropathy was 2%. Twenty-nine partial responses with an objective response rate of 49% were obtained. No complete responses were observed. The median progression-free survival (PFS) and overall survival (OS) were 7.8 and 15.5 months respectively. Cisplatin-based combination chemotherapy at low doses appears to be safe and active in older patients with advanced NSCLC.

Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I-II study.

The aim of this study was to evaluate feasibility and toxicity of escalating doses of epirubicin and paclitaxel plus fixed dose of etoposide and to define the activity of the triplet in extensive disease small-cell lung cancer. Thirteen patients entered the phase I study: the maximum tolerated doses were epirubicin (EpiDX) 90 mg m-2 and paclitaxel (P) 175 mg m-2 with febrile neutropenia as dose-limiting toxicity. The recommended schedule for this regimen for the phase II study was EpiDX 75 mg m-2, P 175 mg m-2, etoposide (E) 100 mg m-2 intravenous (fixed dose) days 1-3 with courses repeated every 21 days. The prophylactic use of colony-stimulating factors (CSFs) was not allowed. Twenty patients entered the phase II trial: median age was 61 years (range 50-70), median Eastern Cooperative Oncology Group performance status 0 (0-2); nine patients had visceral disease and 17 had more than two metastatic sites. A total of 100 courses were administered with a median of 5 (range 1-6) per patients. Main toxicity (NCI-CTC) was myelosuppression: neutropenia grades 3 and 4 in 16 and 35% of the courses, respectively. Seven episodes of febrile neutropenia were documented and one patient required hospital admission. Nonhaematological toxicity was moderate. Seven out of 19 evaluable patients achieved a complete response (37%), nine patients (47.3%) a partial response with an overall response rate of 84.2% (95% confidence interval=60.4-96.6). In this poor prognostic population of patients the triplet epirubicin/paclitaxel/etoposide showed high antitumour activity with mild nonhaematological side effects. The use of CSFs should be able to improve the haematological profile.

Phase II study of neoadjuvant chemotherapy in patients with surgically-proven, unresectable stage III non-small cell lung cancer.

BACKGROUND: The aim of this study was to assess whether patients with truly unresectable (bulky extracapsular N2, T4 for tracheobronchial angle or mediastinal organ invasion) stage III non-small cell lung cancer (NSCLC), as proven by cervical mediastinoscopy supplemented or not by left anterior mediastinoscopy and fiberoptic bronchoscopy or thoracotomy, could become resectable after induction cisplatin-containing chemotherapy. In addition, we studied the value of preoperatory magnetic resonance imaging (MRI), in evaluating the probability of achieving a radical resection after neoadjuvant chemotherapy. PATIENTS AND METHODS: Sixteen consecutive untreated stage III NSCLC patients were enrolled in the study. All the patients received two cycles of combination chemotherapy including cisplatin 100-120 mg/m2 intravenously (i.v.) days 1 and 22 and vinorelbine 30 mg/m2 i.v. days 1, 8, 15, 22 and 28 or vinblastine 5 mg/m2 i.v. days 1, 8, 15, 22 and 28. Thoracotomy was planned, after chemotherapy, for all non-progressive patients. No other treatment after surgery was devised following radical resection and patients with residual disease after surgery received standard post-operative radiotherapy. Response to treatment was evaluated by thorax CT and MRI two weeks after the last administration of chemotherapy. RESULTS: The overall complete resection rate was 38% (6 out of 16 patients). MRI was predictive of complete resectability in 80% of cases. In fact, 6 patients judged resectable were completely resected, 3 patients judged unresectable underwent only explorative thoracotomy or incomplete resection while MRI was unpredictive only in one case. The most important chemotherapy-related toxicity was hematological: eight patients (50%) had grades III-IV leukopenia. CONCLUSION: These results indicate that preoperative second generation cisplatin-based chemotherapy can make resectable truly unresectable stage III NSCLC patients in only 38% of cases and that MRI is a reliable tool for assessment of radical resection probability after neoadjuvant chemotherapy.

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 Simon's 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.

The role of vindesine and lonidamine in the treatment of elderly patients with advanced non-small cell lung cancer: a phase III randomized FONICAP trial. Italian Lung Cancer Task Force.

AIMS: To evaluate the efficacy and treatment compliance in elderly patients with advanced non-small cell lung cancer (NSCLC) of two chemotherapeutic agents with mild toxicity, 153 previously untreated patients aged over 70 years were randomized to receive lonidamine (450 mg daily p.o. until progression), vindesine (3 mg/m2/daily i.v. weekly for 4 weeks and then every 2 weeks until progression), the combination of the two drugs at the same dose and schedule, or supportive therapy only in a four-arm factorial randomized trial. METHODS: 126 patients were included in the final analysis. Their median age was 75 years. Forty percent had stage IV disease and 60% stage III. Most patients were males (85%) and the majority had squamous histology (68%). RESULTS: Among 104 patients evaluable for response there were only 3 PRs (1/30 in the lonidamine arm and 2/33 in the lonidamine + vindesine arm). Overall, 8.7% and 9.5% of the patients, respectively, progressed or died early, before response evaluation; another 9.4% refused treatment continuation because of poor compliance with the study protocol. Eighty-five patients were fully evaluable for toxicity, which was generally mild. Leukopenia grade 1-3 was found in less than 30% of patients treated with vindesine or vindesine + lonidamine. The most common complaints associated with lonidamine treatment were myalgia (70% of patients), fatigue (55% and 83% of patients treated with lonidamine or lonidamine + vindesine, respectively) and testicular pain in nearly 40% of cases. The overall median survival was 170 days, with no significant impact on survival of either lonidamine or vindesine. CONCLUSIONS: The low response rate and survival together with the poor treatment compliance, even in the presence of mild toxicity, do not support the usefulness of these "gentle" chemotherapies in elderly NSCLC patients. The standard management of advanced NSCLC in elderly patients remains to be defined. Specifically designed studies to address this issue are warranted.

Systemic drug therapy of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an uncommon malignancy characterized by a rapid clinical course. Few patients are possible candidates for radical surgery. According to most reviews, radiotherapy has a limited role in the treatment of MPM. The role of chemotherapy in the management of pleural mesothelioma still remains uncertain. The available data indicate that although 10-20% of patients are known to achieve on objective response to a number of chemotherapeutic agents, the impact on survival appears limited and improvement in the quality of life remains uncertain. The results of combination chemotherapy are comparable to those of single-agent chemotherapy and no major difference is detectable among the various combinations. Prospective phase II trials are recommended for the identification of new active treatments while large-scale randomized phase III trials are needed to identify the best available treatment. In addition, new standard criteria for eligibility and response assessment are required. This paper reviews the available literature on the systemic drug therapy of MPM.

Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP).

In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1, ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95% CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase II randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase II trials.

Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: To compare two cisplatin based chemotherapy schedules in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 332 patients with advanced NSCLC were randomized to receive cisplatin 80 mg/m2 on day 1 either in combination with teniposide 100 mg/m2 on days 1, 3, and 5 (arm A) or paclitaxel 175 mg/m2 by 3-hour infusion on day 1 (arm B); cycles were repeated every 3 weeks. RESULTS: Fifteen patients were ineligible; patient characteristics were well balanced between the two arms: 71% were male, 71% had less than 5% weight loss, 89% had a World Health Organization (WHO) performance status of 0 to 1, 51% had adenocarcinoma, and 61% had stage IV disease. Hematologic toxicity was significantly more severe in arm A (leukopenia, neutropenia, and thrombocytopenia grade 3 or 4: 66% v 19%, 83% v 55%, 36% v 2% in arms A and B, respectively), which resulted in more febrile neutropenia (27% v 3% in arms A and B, respectively), dose reductions, and treatment delays. There were a total of nine toxic deaths, six due to neutropenic sepsis: five in arm A and one in arm B. In contrast, arthralgia/myalgia (grade 2 or 3, 4% v 17%), peripheral neurotoxicity (grade 2 or 3, 6% v 29%), and hypersensitivity reactions (1% v 7%, all grades) were significantly more frequent in arm B. The frequency and severity of other toxicities were comparable between the two arms. Responses were one complete and 44 partial on arm A (28%) and two complete and 61 partial (41%) on arm B (P = .018). There was no significant difference in survival, with median and 1-year survivals 9.9 versus 9.7 months and 41% versus 43%, respectively in arm A and B. Progression-free survival was 4.9 and 5.4 months in arm A and B, respectively. Selected centers participated in a quality-of-life (QoL) assessment, which was performed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and LC-13 administered at baseline and every 6 weeks thereafter. Arm B achieved a better score at week 6 for emotional, cognitive and social functioning, global health status, fatigue, and appetite loss, which was lost at 12 weeks. In conclusion, arm B appears superior to arm A with regard to response rate, side effects, and QoL. CONCLUSION: Although survival was not improved, arm B offers a better palliation for advanced NSCLC patients than arm A.

Management of malignant pleural effusions.

Malignant pleural effusions (MPEs) represent a common complication of advanced malignancies. However, adequate palliation of this highly symptomatic accompaniment to cancer can be achieved in most patients by adopting the appropriate therapy. Several options are available for the treatment of MPE. Systemic therapy may control the effusion in patients whose underlying malignancy is sensitive to anti-cancer agents. Repeated thoracocentesis can be appropriate for patients with limited life expectancy or slowly recurrent effusions. In the majority of the remaining cases the treatment of choice is pleurodesis with sclerosing agents administered via tube thoracostomy. Controversy still exists as to which drug produces the best results: talc and bleomycin appear to be among the most cost-effective agents. The debate over the best agent to be used for pleurodesis refers to the difficulty in comparing results of studies using different eligibility criteria, response assessment and end-points. This article describes the various treatments which have been reported in the literature to play a role in the management of MPEs. It is also aimed at providing guidelines in allocating patients to appropriate treatments.

Combined cisplatin, doxorubicin, and mitomycin for the treatment of advanced pleural mesothelioma: a phase II FONICAP trial. Italian Lung Cancer Task Force.

BACKGROUND: In a previous FONICAP trial, the combination of doxorubicin (D) and cisplatin (P) yielded an objective response rate of 25% and a subjective response rate of 50% in patients with mesothelioma. In human mesothelioma cell lines, mitomycin (M) showed a synergic activity with P and in a recent randomized study, the combination of M and P showed slightly superior activity when compared with the PD regimen. METHODS: The authors tested the activity and toxicity of a combination chemotherapy regimen including P, 60 mg/m2, D, 60 mg/m2, and M, 10 mg/m2, all by intravenous infusion on Day 1 every 28 days in a Phase II study. RESULTS: Twenty-four chemotherapy-naive mesothelioma patients were enrolled in the study. Patient characteristics were the following: the median age was 58 years; the median performance status was 1; there were 6 Stage I patients, 15 Stage II patients, 2 Stage III patients, and 1 Stage IV patient; and 10 patients had previous asbestos exposure. All patients had pretreatment symptoms: 13 had chest pain, 9 had pleural effusion, and 7 had dyspnea. A total of 78 cycles of chemotherapy were administered. The only significant side effect was myelosuppression, with only 9.5% of patients having Grade 4 toxicity. Among 23 patients evaluable for response, 5 achieved a partial response (20.8%; 95% confidence interval, 7.1-42.1%), 9 had stable disease, and 9 had progressive disease (including 1 early death). One patient was not evaluable because of treatment refusal. A clinical improvement was observed in 7 of 24 patients (29%). CONCLUSIONS: The combination of PDM in patients with pleural mesothelioma is feasible and moderately active. However, the observed level of activity is similar to that obtained with other two-drug regimens.

Phase I study of simultaneous dose escalation and schedule acceleration of cyclophosphamide-doxorubicin-etoposide using granulocyte colony-stimulating factor with or without antimicrobial prophylaxis in patients with small-cell lung cancer.

A phase I study was designed to assess whether dose intensity of an 'accelerated' cyclophosphamide-doxorubicin-etoposide (CDE) regimen plus granulocyte colony-stimulating factor (G-CSF) could be increased further, in an outpatient setting, by escalating the dose of each single drug of the regimen. Patients with previously untreated small-cell lung cancer (SCLC) received escalating doses of cyclophosphamide (C) 1100-1300 mg m-2 intravenously (i.v.) on day 1, doxorubicin (D) 50-60 mg m-2 i.v. on day 1, etoposide (E) 110-130 mg m-2 i.v. on days 1, 2, 3 and every 14 days for at least three courses. Along with chemotherapy, G-CSF (filgastrim) 5 micrograms kg-1 from day 5 to day 11 was administered subcutaneously (s.c.) to all patients. Twenty-five patients were enrolled into the study. All patients at the first dose level (C 1100, D 50, E 110 x 3) completed three or more cycles at the dose and schedule planned by the protocol and no 'dose-limiting toxicity' (DLT) was seen. At the second dose level (C 1200, D 55, E 120 x 3) three out of five patients had a DLT consisting of 'granulocytopenic fever' (GCPF). Another six patients were treated at this dose level with the addition of ciprofloxacin 500 mg twice a day and only two patients had a DLT [one episode of documented oral candidiasis and one of 'fever of unknown origin' (FUO) with generalised mucositis]. Accrual of patients proceeded to the third dose level (C 1300, D 60, E 130 x 3) with the prophylactic use of ciprofloxacin. Four out of six patients experienced a DLT consisting of GCPF or documented non-bacterial infection. Accrual of patients at the third dose level was then resumed adding to ciprofloxacin anti-fungal prophylaxis (fluconazole 100 mg daily) and anti-viral prophylaxis (acyclovir 800 mg twice a day) from day 5 to 11. Out of five patients treated three experienced a DLT consisting of severe leucopenia and fever or infection. With a simultaneous dose escalation and schedule acceleration it is indeed possible to take maximum advantage of G-CSF activity and to increase CDE dose intensity by a factor 1.65-1.80 for a maximum of 3-4 courses. The role of antimicrobial prophylaxis in this setting deserves to be investigated further.

Paclitaxel for malignant pleural mesothelioma: a phase II study of the EORTC Lung Cancer Cooperative Group.

The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma. Paclitaxel was given intravenously at a dose of 200 mg m-2 as a 3 h infusion every 3 weeks, after standard premedication with corticosteroids and antihistamines. This regimen was well tolerated, with < 4% of cycles resulting in severe toxicity. No major objective responses were observed and ten patients had stable disease. Median survival time was 39 weeks and the 1 year survival rate was 30%. In conclusion, paclitaxel at the dose and schedule investigated in this trial had no major activity in the treatment of malignant pleural mesothelioma.

Mitomycin-ifosfamide-cisplatinum (MIP) vs MIP-interferon vs cisplatinum-carboplatin in metastatic non-small-cell lung cancer: a FONICAP randomised phase II study. Italian Lung Cancer Task Force.

The FONICAP group is screening, with randomised phase II studies, the activity of new chemotherapy programmes for advanced non-small-cell lung cancer (NSCLC) looking for regimens with > 30% activity. In the present study, three regimens were tested: MIP (mitomycin 6 mg m-2, ifosfamide 3 g m-2, cisplatinum 80 mg m-2 on day 1 every 28 days); MIP-IFN (MIP and interferon alpha-2b 3 MU s.c. three times a week); and PC (cisplatinum 60 mg m-2 and carboplatin 400 mg m-2 on day 1 every 28 days). Overall 93 chemotherapy-naive patients were enrolled: 23 received MIP, 27 received MIP-IFN and 43 received PC. Eighty per cent of the patients had stage IV and 20% stage IIIb disease (positive pleural effusion or supraclavicular nodes). Response rates were as follows: MIP = 9% (95% CI 1-28%), MIP-IFN = 7% (95% CI 1-24%) and PC = 14% (95% CI 5-28%). The overall median survival was 183 days. Grade III-IV leucopenia was observed in 36% of patients treated with MIP-IFN vs 10% in the other two arms, and thrombocytopenia grade III-IV was reported in nearly 10% of patients overall. In conclusion, (1) all three regimens investigated have poor activity (< 30%); (2) when tested in multicentre randomised phase II trials, MIP displays lower activity than in phase II trials; (3) PC has similar activity to other platinum-containing regimens; (4) randomised phase II studies are a reliable and quick method of determining the anti-tumour activity of novel chemotherapeutic regimens in NSCLC.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) allows acceleration and dose intensity increase of CEF chemotherapy: a randomised study in patients with advanced breast cancer.

A randomised study was conducted in 62 patients with advanced breast cancer to assess whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would yield an increase in the dose intensity of a standard-dose CEF regimen through an acceleration of chemotherapy administration. Patients received CEF (cyclophosphamide 600 mg m-2, epidoxorubicin 60 mg m-2 and fluorouracil 600 mg m-2) i.v. on day 1 or the same chemotherapy, plus GM-CSF 10 micrograms kg-1 s.c. starting from day 4, repeated as soon as haematopoietic recovery from nadir occurred. Patients in the CEF + GM-CSF group received chemotherapy at a median interval of 16 days compared with 20 days in the control group. This led to a significant increase (P = 0.02) in the dose intensity actually administered in the third, fourth and sixth cycles: +28%, +25%, +20% respectively. Non-haematological toxicity was mild. GM-CSF had to be reduced or suspended in 50% of patients because of toxicity. Haematological toxicity, mainly cumulative anaemia and thrombocytopenia, was manageable. An increase in response rate for patients with measurable disease, of borderline statistical significance (P = 0.088, P for trend = 0.018), from 42% in the CEF group to 69% in the CEF + GM-CSF group, was observed. This randomised trial indicates that GM-CSF is useful for chemotherapy acceleration. Accelerated CEF + GM-CSF is a moderately dose-intensive regimen that can be administered in an outpatient clinic and is associated with a high objective response.

Recombinant interferon alpha-2b in the treatment of diffuse malignant pleural mesothelioma.

Fourteen patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II study to assess activity and toxicity of the systemic administration of recombinant (r)-alpha-interferon (IFN)-2b. The IFN schedule was: 3 x 10(6) IU i.m. days 1-4, 6 x 10(6) IU days 5-8, 10 x 10(6) IU days 9-12; then IFN was administered at 10 x 10(6) IU 3 days/week. If grades II-III toxicity occurred, IFN dose was reduced and drug continued at the previous dose level. All patients were evaluated by CT scan. Only one patient was not evaluable for response and toxicity because of inadequate follow-up. Of 13 evaluable patients, we observed 1 objective response, 6 stable disease, and 6 failures (3 progressive disease and 3 early interruptions due to subjective toxicity). The median time to progression was 19 weeks, and the median overall survival was 62 weeks. Toxicity was mild: of 13 patients evaluable for toxicity we observed fever (9 patients), flu-like syndrome (3 patients), fatigue (4 patients), anorexia (2 patients), myelosuppression (3 patients), and muscle pain (1 patient). The results of this study indicate only marginal activity of r-alpha-IFN in the treatment of DMPM.

Combination of chemotherapy and recombinant alpha-interferon in advanced non-small cell lung cancer. Multicentric Randomized FONICAP Trial Report. The Italian Lung Cancer Task Force.

BACKGROUND: Preclinical data suggested that alpha-interferon (IFN) may potentiate chemotherapy cytotoxicity. METHODS: A prospective multicentric randomized trial was initiated to assess the clinical benefit of adding recombinant alpha-2-IFN to combination chemotherapy in patients with metastatic non-small cell lung cancer. A total of 182 patients were randomized to receive either cisplatin-epidoxorubicin-cyclophosphamide (CEP) combination chemotherapy (cisplatin, 60 mg/m2; epidoxorubicin, 50 mg/m2; and cyclophosphamide, 400 mg/m2 intravenously) alone on day 1 or the same chemotherapy plus recombinant alpha-2-IFN at the dose of 5 MU intramuscularly from day -2 to +4, then 3 times weekly. RESULTS: The median survival was 6 months in the CEP plus IFN arm versus 5.5 months in the control arm. The log-rank test showed a marginal statistically significant difference (P = 0.045) in favor of CEP chemotherapy, which disappeared when survival curves were adjusted for prognostic factors. Progression-free survival was similar in the two treatment arms. Considering all eligible patients, the response rate was 7.6% in the CEP arm versus 18.9% in the CEP plus IFN arm (P = 0.042). Nearly 40% of the patients receiving IFN had grade 3-4 nadir leukopenia versus 15% in the control arm (P = 0.01) and 12.5% versus 4.2% had grade 3-4 thrombocytopenia. Apart from the usual constitutional symptoms, IFN was also responsible for increased emesis and mucositis. CONCLUSIONS: This study indicates that the addition of recombinant alpha-IFN to CEP chemotherapy can increase response rate and toxicity to treatment without a positive effect on progression-free survival and survival.

High dose-intensity chemotherapy, with accelerated cyclophosphamide-doxorubicin-etoposide and granulocyte-macrophage colony stimulating factor, in the treatment of small cell lung cancer.

15 patients with small-cell lung cancer were treated with an "accelerated" chemotherapy consisting of standard-dose cyclophosphamide-doxorubicin-etoposide administered every 15 days (as opposed to the usual 21-day intervals) along with granulocyte-macrophage colony stimulating factor (10 micrograms/kg/day) administered prophylactically subcutaneously from day 4 to 13. The primary objective of this study was to examine the possibility of achieving a 50% dose-intensity increase by a shortening of chemotherapy intervals. 9 patients were not able to complete the planned six courses of chemotherapy owing to cumulative haematological toxicity. In fact, while leukopenia was acceptable and constant during treatment, both thrombocytopenia and anaemia progressively worsened with subsequent courses, becoming particularly severe after the 4th cycle when interruption of the treatment was often required. 13 patients who completed four courses of chemotherapy received a median of 96% of the planned dose-intensity. This corresponded with an average relative dose-intensity actually delivered of 1.44 compared with the planned dose-intensity of a standard cyclophosphamide-doxorubicin-etoposide every 21 days. In conclusion, acceleration of cyclophosphamide-doxorubicin-etoposide chemotherapy combined with granulocyte-macrophage colony stimulating factor can lead to a significant increase of dose-intensity but it is feasible only for a limited number of courses.

A pilot study of mitomycin, ifosfamide and cisplatin as outpatient combination chemotherapy for advanced non-small cell lung cancer.

Twenty-one patients with advanced stage, non-small-cell lung carcinoma were treated with a chemotherapy regimen including: mitomycin (6 mg/m2), ifosfamide (3 g/m2), cisplatin (80 mg/m2). The regimen was administered on an outpatient basis. Two patients were lost to follow-up. Among the 29 patients evaluable for response we registered a response rate of 36.8%; 36.8% of patients had stable disease, and 15.7% progressed during treatment. Median duration was 8.7 months and median survival was 11 months. Toxicity was low and easily manageable on an out-patient basis.

Activity of doxorubicin and cisplatin combination chemotherapy in patients with diffuse malignant pleural mesothelioma. An Italian Lung Cancer Task Force (FONICAP) Phase II study.

Twenty-six symptomatic patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II Italian Lung Cancer Task Force (FONICAP) study to assess the activity and toxicity of doxorubicin and cisplatin combination chemotherapy. The drug schedule was as follows; 60 mg/m2 of doxorubicin and 60 mg/m2 of cisplatin both given intravenously (IV) on day 1 every 3 to 4 weeks. Of the 24 evaluable patients, 6 objective partial responses (25%; 95% confidence limits, 9.77% to 46.71%) were observed. Twelve of 24 patients (50%), including 6 with no radiologic evidence of response, had a clinical improvement as demonstrated by an objective reduction of symptom or performance status scores along treatment. The overall median survival time was 10 months. Toxicity was mild and dose reductions or suspensions were not required. The combination of doxorubicin and cisplatin is effective and well tolerated. It might be considered for palliation of symptomatic patients with DMPM.