ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients.

BACKGROUND: Lymphopenia is a predictive factor for hematological toxicity, progression and early death in advanced cancers including metastatic breast cancer (MBC). CYT107 is a recombinant interleukin 7 (IL-7) (Cytheris, now Revimmune), well tolerated and able to expand lymphocyte pool in humans. The aims of this study were to determine the optimal schedule to deliver CYT107 and to assess its effect on clinical end points. PATIENT AND METHODS: This placebo-controlled, double blind, phase IIa was conducted in MBC patients with <1500/µl lymphocytes treated with capecitabine. Using a 2-by-2 factorial design, 20 patients were randomly allocated to four arms to receive (i) before chemotherapy: CYT107 or placebo; then (ii) during chemotherapy: CYT107 or placebo. The primary end point was CD4+ count changes before and during chemotherapy. Secondary end points were hematological toxicity, safety, overall response, progression-free survival (PFS) and overall survival (OS). Quantification and functional competence of circulating immune cells were also assessed. RESULTS: When administered before chemotherapy, CYT107 induced a significant increase of CD4+ [+148.1% in CYT107 versus +9.9% in placebo groups, (Wilcoxon, P = 0.002)] and CD8+ T-cell counts, including both naïve and memory subsets. When CYT107 was administered during chemotherapy, the magnitude of CD4+ and CD8+ increase was less important. No modulation of immune cell functional competence was observed. CYT107 was well tolerated with no related ≥grade 3 adverse events except 1 fatal suspected unexpected serious adverse reaction (SUSAR) of uncertain relationship. Of the 12 cases evaluable for response, 6 of 7 patients (86%) receiving CYT107 before chemotherapy achieved a response or stabilization, whereas two of five patients (40%) receiving placebo achieved the same result. No significant difference was observed for PFS or OS. CONCLUSION: In lymphopenic MBC, CYT107 increases CD4+ and other T-cell subset counts without altering their function. A larger clinical trial to demonstrate its impact on clinical outcome is warranted. CLINICALTRIALSGOV IDENTIFIER: NCT01362107.

Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group phase II trial of first-line irinotecan in patients with advanced or recurrent squamous cell carcinoma of the cervix.

PURPOSE: To determine the efficacy and tolerability of irinotecan (CPT-11) in advanced or recurrent cervical carcinoma. PATIENTS AND METHODS: Eligible patients had histologically confirmed, inoperable, progressive, metastatic or recurrent squamous cell cervical carcinoma and had received no radiotherapy in the preceding 3 months and had never received chemotherapy. The initial irinotecan dosage of 350 mg/m(2) every 3 weeks was modifiable according to toxicity. Treatment continued for six cycles after complete response, or until disease progression or excessive toxicity after partial response, or for three additional cycles in the case of stable disease. Patients were stratified into group A (>/= one measurable lesion in a previously unirradiated area, with or without progressive disease in irradiated fields) or group B (measurable new lesion[s] in an irradiated field). RESULTS: Fifty-one of 55 enrolled patients were eligible for inclusion (median age, 47 years; range, 30 to 71 years). The response rate was 15.7% (95% confidence interval [CI], 7.0% to 28.6%) overall, 23.5% (95% CI, 10.7% to 41.2%) for group A (complete response, 2.9%), and zero for group B. The median time to progression and median survival were 4.0 and 8.2 months for group A and 2.5 and 4.2 months for group B, respectively. The major grade 3/4 toxicities for groups A and B were diarrhea (24.3% and 55.5%, respectively) and neutropenia (24.3% and 33.3%, respectively). There were four toxicity-related deaths, three in group B. Patients with no prior external pelvic irradiation experienced fewer grade 3 and 4 adverse events. CONCLUSION: Irinotecan is effective in treating cervical squamous cell carcinoma if disease is located in an unirradiated area. Because of toxicity, a reduced dose is advised for patients previously treated with external pelvic irradiation.

Interleukin-2 with and without LAK cells in metastatic renal cell carcinoma: the Lyon first-year experience in 20 patients.

Thirty-one patients with metastatic renal cell carcinoma were seen at the Centre Léon Bérard from October 1987 to October 1988. According to our protocol, 11 were excluded leaving 20 in the study. The median age was 55 years (range 36 to 79 years). The median number of metastases was 9 (range 2 to 29) and the median number of metastatic sites was 3 (range 1 to 4). Seventeen patients received a continuous infusion of recombinant interleukin-2 (rIL-2) of 3 x 10(6) U/m2/day, on days 1 to 5, with lymphapheresis on days 7 to 10 and IL-2 + LAK on days 11 to 15. Three patients received IL-2 alone. The clinical toxicity of IL-2 was as expected (100% fever, 88% erythema, 88% vomiting, 87% weight gain, 76% oliguria, 76% diarrhoea, 70% pruritus, 70% weakness, 41% severe hypotension, 41% acute renal failure, 33% disorientation, 23% respiratory distress, 12% ventilation and 5% coma) with no toxic deaths. Other toxicity was mild (median platelet nadir was 93,000 and median nadir of Hb 8.1 g/dl) except for the creatinine level which was found to be between 200 and 400 mumol/l in 45% of the courses and over 400 mumol/l in 24% of the courses. Eight capillary leak syndromes were observed. Among the three patients receiving IL-2 alone, one PD, one SD and one early toxicity were recorded. Among 15 evaluable patients receiving IL-2 + LAK, three had PR (20%) and two mixed response (PR and progression before 2 months); two had stable disease and eight had progression. No clinical or biological factor was able to predict response. However, the five objective responses were observed among the eight patients with a capillary leak syndrome. Lymphocyte peaks or platelet nadir were not related to response in this group of patients. The median number of harvested mononuclear cells was 9.8 x 10(10) and the median number of mononucleated cells reinjected was 5.9 x 10(10).

Pharmacokinetically guided dosing for intravenous melphalan: a pilot study in patients with advanced ovarian adenocarcinoma.

Pharmacokinetically guided administration of melphalan was investigated during a pilot study in patients with advanced ovarian adenocarcinoma. The schedule involved a fixed dose on day 1 (7.9 mg) followed by a second dose on day 2, calculated on the basis of pharmacokinetic data to achieve a target area under the concentration-time curve (AUC). 20 courses of intravenous melphalan were administered to 7 patients. AUC, standardised to 1 mg/m2, ranged between 4.3 and 8.9 (mg/l) min. In 12 fully evaluable courses, less than 15% deviation from the target AUC was found, showing that AUC monitoring was possible by means of the test dose. Pharmacodynamic effects showed a positive correlation with melphalan AUC. Myelosuppression appeared at 47 (mg/l) min and grade 3 or 4 haematological toxicities were observed in 4 cycles, associated with AUC values ranging between 86 and 112 (mg/l) min. Relative leucocyte decreases were well correlated with AUC values.

Phase II study of cystemustine in metastatic colorectal carcinoma. A trial of the EORTC Clinical Screening Group.

27 patients with metastatic colorectal carcinoma were treated, every 2 weeks, with 60 mg/m2 cystemustine, a new chloro-2-ethyl nitrosourea derivative. Haematological toxicity was the major side-effect including neutropenia and thrombocytopenia. We did not observe any complete or partial response. Cystemustine, with this dose and this schedule, has no activity in colorectal cancer.

Pretreatment staging evaluation in small cell lung carcinoma. A new approach to medical decision making.

The real need for extensive staging at the time of diagnosis is discussed in regard to small cell lung carcinoma. We performed a decisional retrospective analysis on a series of 182 patients, based on three staging steps: the first step included physical examination and routine biologic tests. The second step consisted of liver ultrasonography and needle aspiration of any clinically detectable tumor mass, and the third step included bone marrow examination, radionuclide bone scan, thoracic, abdominal, and brain CT scan. A stepwise multivariate logistic regression performed on 11 variables considered in the first step shows that a four-parameter model can predict the spread of the disease (limited or extensive): weight loss, performance status, and elevated LDH or alkaline phosphatase levels. Limited disease can be predicted in two ways: (1) elevated LDH with normal alkaline phosphatases, no weight loss, and good performance status, or (2) normal LDH and alkaline phosphatases. In this series, 28 percent of patients can be predicted as having extensive disease and can be treated with chemotherapy alone without chest irradiation. After the second step, the probability of disease being extensive is only 25 percent, and only 84 (46.15 percent) patients would need to undergo the third step of staging procedures (brain CT scan, bone marrow aspiration and biopsy, radionuclide bone scan) with this method. We conclude that a multistep approach represents a simple staging method and offers the advantage of harmlessness and lower costs for patients not to be evaluated in prospective clinical trials.

Dose-finding, pharmacokinetic and phase II study of docetaxel in combination with gemcitabine in patients with inoperable non-small cell lung cancer.

BACKGROUND: The good efficacy-toxicity ratio of both docetaxel and gemcitabine in non-small cell lung cancer (NSCLC) stimulates the investigation of the combination of these drugs as a first line chemotherapy. This two-step study firstly aimed at determining the maximum tolerated and recommended doses of docetaxel given every 3 weeks in combination with a fixed dose of gemcitabine; the phase I study paid particular attention to pharmacokinetics. Afterwards, the safety and efficacy of the recommended dose was carefully assessed in the phase II-step. METHODS: The following range of docetaxel dosages were tested in the phase I study; 60, 75, 85, and 100 mg m(-2) given on day 8 in combination with gemcitabine 1000 mg m(-2) delivered on days 1 and 8 of a 3-week cycle. Haematopoietic growth factors were not allowed. The treatment was delivered on an outpatient basis. Main eligibility criteria consisted of stage III b or IV histologically proven NSCLC, Eastern Co-operative Oncology Group (ECOG) performance status PS < or =2, age < or =70 years, measurable disease, adequate blood counts, chemistry, and no symptomatic brain metastasis. RESULTS: Four centres enrolled 49 patients (eight having been pre-treated); 16 in phase I and 33 in phase II. The maximal tolerated dose was almost reached at the last dose level (i.e. docetaxel, 100 mg m(-2)). Consequently, we considered the 85 mg m(-2) level as the recommended dose. There was a positive relationship of the docetaxel dose to the area under the curve of this drug. Toxicity was assessable in all patients. Among the 200 cycles delivered, 192 were assessable for this feature. Main toxicity was grade 3-4 neutropenia affecting 23 patients (47% of the population; 23% of the cycles). Six febrile episodes were recorded leading to two treatment-related deaths. Another patient died from congestive cardiac failure. In addition, six patients experienced interstitial pneumonitis, (one half considered as severe), two of them having received the recommended dose. All patients recovered from this toxicity after corticosteroids. Fourteen patients out of the whole population (29%; 95% CI [17-43], including ten patients receiving the recommended dose), achieved an objective response. Median follow-up was 14 months (range, 0.3-29.4). Median survival was 11.2 months (95% CI [8.3-13.2]), and the 1-year survival rate was 45%. CONCLUSION: Gemcitabine, 1000 mg m(-2) days 1 and 8 in combination with docetaxel, 85 mg m(-2), day 8, given every 3 weeks could be considered as an active regimen with manageable toxicities in locally advanced or metastatic NSCLC. This study deserves further comparisons with classical platinum-based regimens.

The prognostic value of etoposide area under the curve (AUC) at first chemotherapy cycle in small cell lung cancer patients: a multicenter study of the groupe Lyon-Saint-Etienne d'Oncologie Thoracique (GLOT).

PURPOSE: To assess the potential relationships between systemic exposure to doxorubicin, etoposide and ifosfamide at first chemotherapy cycle and therapeutic effect, tumor response, toxicity, and survival, in small cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Twenty-four patients referred to five different centers with either thorax-limited or metastatic SCLC entered the study. All but one received two induction courses of the 3 day-AVI (doxorubicin 50 mg/m(2) day 1, etoposide 120 mg/m(2) day 1, 2, 3, ifosfamide 2000 mg/m(2) day 1, 2) regimen. Individual plasma samples were collected at the first course and complete concentration data on 24 courses were available. Drugs exposures were estimated using a population pharmacokinetic method and expressed as clearance (Cl), area under the curve (AUC), and AUC-intensity (AUC/cycle duration). Responding patients received thoracic irradiation+concomitant cisplatinum-etoposide (limited disease) or four more courses of AVI (extensive disease). The impact of exposure parameters on haematological toxicity, tumor response and overall survival was assessed using linear regression, the Mann-Whitney U-test and the log-rank test/Kaplan-Meier estimation, respectively. RESULTS: Twenty-three patients could be evaluated for response and survival. We found no relationship between drug exposure and haematological toxicity but all patients had received Granulocyte-Colony Stimulating Factor support. Tumor response was marginally influenced by ifosfamide AUC. In patients with etoposide AUC>254.8 mg h/l, 1-year survival was 50.0 vs. 9.1% in the other group (median 11.4 vs. 7.1 months, P=0.02), with respect to established prognostic factors. In patients with extensive disease only (n=15), 1-year survival was 42.9 vs. 0% (median 11.3 vs. 5.3 months, P=0.01). CONCLUSION: This study strongly suggests that SCLC patients should benefit from sufficient etoposide exposure at first cycle to improve survival. Adaptative control based on plasma concentration measurements should be tested in further studies assessing various polychemotherapy regimens.

Intravenous interleukin-2 just after high dose BCNU and autologous bone marrow transplantation. Report of a multicentric French pilot study.

This multicentric pilot study was conducted in order to evaluate the feasibility of early interleukin-2 (IL2) after high dose chemotherapy requiring autologous bone marrow transplantation (ABMT). BCNU at 800 mg/m2 was followed, 3 days later, by the reinjection of the bone marrow cells. At day 4, IL2 at 18 x 10(6) i.u./m2/day was given as a continuous infusion during a minimum of 6 days (first phase of study) or for 6 more days after 1 day break (second phase of the study). Twenty patients were included. Toxicity was not negligible, with one toxic death, but IL2 therapy does not damage the haematological recovery of most patients. However, a 6-day IL2 treatment period only appears tolerable. In 18 evaluable patients, three responses were observed: one complete response (CR) of short duration in a non-Hodgkin's lymphoma, one CR (24 months +) and one partial response (PR) (6 months) in two patients with metastatic gastric adenocarcinoma. This study confirms that IL2, restricted to a 6-day treatment period, is feasible immediately after high-dose chemotherapy requiring ABMT without haematological problem in most patients. The response rate was unexpected for a pilot study and this combined therapy obviously requires further study.

Pharmacokinetics of high-dose intravenous melphalan in children and adults with forced diuresis. Report in 26 cases.

The pharmacokinetic parameters of the alkylating agent melphalan were determined in 15 children and 11 adults with advanced malignant solid tumors. High IV bolus doses of 140 mg/m2 were given under standard hyperhydration conditions and followed by autologous bone marrow grafting. In all cases the time-concentration curves could be best fitted to a biexponential pattern. A high scattering of drug concentrations was observed in our patients, the disposition half-lives ranging in the whole group from 17.8 to 71.2 min. The areas under the curves also showed a wide variation, ranging from 175 to 682 mg 1(-1) min-1. In all patients, melphalan levels in plasma were unmeasurable at 8 h or earlier, indicating that bone marrow can be safely reinfused at that time. No difference was apparent between children and adults regarding the drug pharmacokinetics. In each of 11 cerebrospinal fluid samples drawn 45-150 min after melphalan administration, drug levels were unmeasurable.

Phase II study of fotemustine as second-line treatment after failure of immunotherapy in metastatic renal cell carcinoma.

Sixteen patients who after prior systemic immunotherapy had progressing disease received fotemustine (100 mg/m2) i.v. on days 1, 8, and 15 followed by a 5-week rest period. In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 fotemustine given once every 3 weeks until progression on toxicity occurred. No objective response was observed. Four patients showed stable disease (median duration: 4 months; range: 3-19). The main toxicities were neutropenia (WHO grade 3 and 4: 27%) and thrombocytopenia (WHO grade 3 and 4: 27%). Fotemustine was administered on an outpatient basis and was generally well tolerated, but in our series of patients it had no antitumour activity in metastatic renal cell carcinoma after failure of immunotherapy.

In vivo measurement of myocardial oxidative metabolism and blood flow does not show changes in cancer patients undergoing doxorubicin therapy.

PURPOSE: The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. METHODS: Six female non-heart-failure cancer patients treated with doxorubicin were included in a longitudinal study. Resting radionuclide cineangiography and PET scanning with carbon-11 acetate were performed the day before the initiation of doxorubicin treatment at a dosage of 50 mg/m2 every 3 weeks, and 3 weeks after the cumulative administration of 300 mg/m2 (chronic toxicity). In addition, PET was performed 24 h after the first administration of doxorubicin (evaluation of acute toxicity). Myocardial oxidative metabolism and blood flow were assessed by PET (acute and chronic toxicity), and left ventricular ejection fraction was measured by radionuclide angiography (chronic toxicity). RESULTS: Using PET for both acute and chronic toxicity evaluations, no significant effect of doxorubicin was observed either on the flux through the tricarboxylic acid (TCA) cycle or on myocardial blood flow. However, systolic left ventricular function showed a small but significant impairment after the administration of 300 mg/m2 of doxorubicin. CONCLUSIONS: Other hypotheses should be explored to better explain the predominant mechanisms of the cardiotoxicity of anthracyclines in humans.

Phase I clinical and pharmacokinetic study of S9788, a new multidrug-resistance reversal agent given alone and in combination with doxorubicin to patients with advanced solid tumors.

PURPOSE: The objectives of this phase I study were to evaluate the toxic effects and the maximum tolerated dose (MTD) of S9788, a new modifier of multidrug resistance (MDR), when given alone and in combination with doxorubicin to patients with advanced solid tumors; to achieve a potentially active plasma concentration of S9788; and to study the pharmacokinetics of both drugs. METHODS: A total of 26 patients (median age 58 years) entered the study. S9788 was given alone as a 30-min infusion at day 1 and in combination with a 50-mg/m2 bolus of doxorubicin at days 8 and 29. Dose levels of S9788 were escalated from 8 to 96 mg/m2 according to the modified Fibonacci scheme. Plasma samples were taken predose as well as during and up to 48 h after the beginning of infusion for S9788 and doxorubicin quantitation. Fractionated urine samples were also collected for up to 24 h for S9788 determination. RESULTS: The dose-limiting side effects of S9788 consisted of bradycardia, sometimes associated with faintness or dizziness. The MTD of S9788 was 96 mg/m2. No enhancement of doxorubicin toxicity was observed. One partial response (duration 140 days) was observed at 96 mg/m2 in a patient with multiple lung metastases from a refractory urothelial carcinoma. Pharmacokinetic studies were performed in 24 patients. Since the mean apparent elimination half-life of S9788 was 46 +/- 23 h and the last plasma sampling time was 48 h, only model-independent parameters were considered. Plasma levels of S9788 were below the limit of quantitation (4 x 10[-3] microM) before each drug administration. S9788 plasma levels of up to 3.7 microM could be obtained with this administration schedule. The urinary elimination of the unchanged drug was negligible, whatever the collection period. In spite of the large inter- and intraindividual variability, plasma pharmacokinetics of S9788 given as a 30-min i.v. infusion were linear up to 96 mg/m2 and were not modified by doxorubicin administration. Doxorubicin pharmacokinetic parameters did not seem to be influenced by S9788 coadministration. CONCLUSION: The dose-limiting toxicity of S9788 consisted of bradycardia or clinical symptoms suggesting a vasovagal impact such as faintness or dizziness. The MTD of S9788 was 96 mg/m2. The pharmacokinetic parameters of doxorubicin in this study were close to those usually described and were not influenced by escalation of the S9788 dose. No pharmacokinetic interaction was observed between S9788 and doxorubicin. The clinical tolerability of the combined treatment is in good agreement with the pharmacokinetic findings, since no enhancement of doxorubicin toxicity was observed.

Multicentric phase II study of cisplatin and etoposide in patients with metastatic carcinoma of unknown primary.

The aim of this study was to determine the efficacy and toxicity of combination cisplatin and etoposide chemotherapy in patients with metastatic carcinoma of unknown primary. Patients were treated with cisplatin (100 mg/m2 iv day 1) followed by etoposide (100 mg/m2 iv days 1-3) every 3 weeks for a maximum of 6 cycles. Patients with progressive disease after two or four courses could receive FAC (fluorouracil, doxorubicin, and cyclophosphamide) until progression. Twenty-five patients were entered and were assessable for response and toxicity. Fifteen (60%) patients had adenocarcinomas. Patients received a median of four courses. Toxicity was mainly hematologic including grade III/IV neutropenia. The overall response rate was 32%. There was no complete response, 32% partial responses, 32% stable disease, and 36% disease progression. Median response duration was 4 months (range: 2-5 months). The median overall survival of the 25 patients was 8 months. No objective response could be obtained with FAC, but 33% of patients achieved stabilization of the disease for at least 3 months. This cisplatin-etoposide combination demonstrated some activity against an usually resistant disease.

Phase II trials of tetrahydropyranyl-adriamycin (Pirarubicin) on renal and colon carcinoma, melanoma, and soft tissue sarcoma.

Eighty patients with measurable metastatic colon or renal cancer, melanoma, or sarcoma entered these Phase II studies. A dose of 25 mg/m2/day of Pirarubicin (THP) for 3 consecutive days every 4 weeks for the first patients, and then 20 mg/m2/day for 3 days every 3 weeks was given by i.v. push. These patients received 225 cycles for a median cumulative dose of 165 mg/m2 (range: 55-630). The mean number of cycles given was 2.8 (range: 1-8). Only 3 partial responses and 18 stable disease (22%) were observed. Hematologic toxicity was the main problem; it was responsible for one death and a 19% and 44% incidence of grade 3 and 4 WHO neutropenia, respectively. Alopecia was rare (4%). Chemotherapy was discontinued in three cases because of suspicion of cardiac toxicity, but only one patient had a significant drop in left ventricular ejection fraction at a cumulative THP dosage of 120 mg/m2. A lack of efficacy in renal and colon cancer and melanoma was presupposed and confirmed by these trials. Due to pretreatment with anthracycline in most patients, definite evaluation of THP in soft tissue sarcoma could not be given.

[Mucoepidermoid bronchial tumors. General review apropos of 2 new cases]. / Tumeurs mucoépidermoïdes bronchiques. Revue générale à propos de deux nouvelles observations.

Muco epidermoïd tumors of the lung are rare tumors, derived from the minor salivary gland tissue of the proximal tracheo bronchial tree. We distinguish high grade and low grade malignity tumors. Authors are presenting two cases reports of mucoepidermoid tumors of the lung with a very aggressive behavior and a review of the literature. Attention is drawn to the difficult differential diagnosis with adenosquamous carcinoma of the lung.

[Chemotherapy of cancer of the breast in the metastatic phase]. / La chimiothérapie du cancer du sein en phase métastatique.

Metastatic breast adenocarcinoma is a very chemosensitive tumor. Polychemotherapy (CT) is more active than mono-CT inducing a 50-60% response rate in naive chemotherapy patients. The response rate is increased by adding hormonotherapy (HT) to CT in hormone-receptors positive patients. Whether or not HT and CT should be concomitant or consecutive is still questionable. The overall survival remains poor (22-30 months) and no improvement happened during the last decades. A hope for the future is possible from 2 different concepts: high dose chemotherapy or intermittent CT with successive short inductions treatment and no maintenance therapy.

[Comparison of 2 cisplatin and etoposide dosages in relapsing small cell lung cancer]. / Comparison de deux dosages de cisplatine et étoposide dans le cancer bronchique à petites cellules en rechute. (Groupe lyonnais d'oncologie thoracique).

The synergistic combination of cisplatinum and etoposide appears as the best second line treatment in patients relapsing from small cell lung carcinoma (SCLC). In order to test the dose-effect relationship of cisplatinum and etoposide in this situation, we have performed a randomised phase II trial comparing 2 five-day regimens: cisplatinum 20 mg/m2/day+etoposide 60 mg/m2/day (arm A) versus cisplatinum 40 mg/m2/day+etoposide 100 mg/m2/day (arm B) every 4 weeks. Thirty-seven patients were included (arm A: 18, arm B: 19), and 32 were considered to be eligible (arm A: 15, arm B: 17). Eight patients were non evaluable, five of them because of toxic death occurring prior to the second course (arm A: one from neutropenia; arm B: three from neutropenia and one from thrombopenia). The two groups were well balanced with regard to the main prognostic factors (age, sex, performance status, LDH level, response to induction chemotherapy). An objective response was observed in 10/24 evaluable patients (arm A: 4, arm B: 6) and was considered as complete in one patient in arm A and in 2 pts in arm B; these two patients presented with cerebral metastases and their response lasted 9 and 15 weeks respectively. The mean duration of response was 11 weeks in arm A and 10.5 weeks in arm B. The median actuarial survival of the overall population of eligible patients was 15 weeks: 13 weeks in arm A and 16.5 weeks in arm B. The study was discontinued because of the 23.5% toxic deaths rate in the high doses arm in this heavily pre-treated population of patients. However, the high response rate (54% overall, 35% considering toxic death as a failure) is impressive and presents evidence for the dose/effect relationship in SCLC.

[Results of a combination of platinum-vindesin-ametycin-bleomycin (CEMB) in the treatment of stage IV non-small-cell lung cancers]. / Résultats de l'association platine-vindésine-amétycine-bléomycine (CEMB) dans les cancers du poumon non à petites cellules de stade IV.

From July 1987 to July 1988, 35 patients with non small cell lung cancer, stage IV, were included in a phase II trial (GLOT NPC 87/01). The treatment was as follows: cisplatin 50 mg/m2 day 1, vindesin 3 mg/m2 day 1, mitomycin 6 mg/m2 day 2, and bleomycin 15 mg/day, day 1 + 2 by continuous infusion. The evaluation for response was assessed after three courses of chemotherapy. The results were poor: an objective response was observed in three patients: three partial responses and no complete response. Because of tumor progression (18 patients) or toxicity (three patients), 21 patients did not complete the three cycles of chemotherapy. The median survival rate was 100 days. Toxicity was mild: grade III neutropenia occurred in one patient, grade IV thrombocytopenia was also observed in one patient. We conclude that this treatment has only a poor efficacy in stage IV non small cell lung cancer.