Alternating radiotherapy and chemotherapy in limited disease small cell lung cancer.

In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.

A phase II trial of radiochemotherapy with daily carboplatin, after induction chemotherapy (carboplatin and etoposide), in locally advanced nonsmall-cell lung cancer: final analysis.

PURPOSE: To evaluate feasibility and efficacy of concomitant radiochemotherapy (CRCT) in Stage IIIB nonsmall-cell lung cancer (NSCLC), two induction chemotherapy cycles combining etoposide and carboplatin were first delivered, followed by CRCT with daily radiation fraction in association with carboplatin. METHODS AND MATERIALS: Forty patients with biopsy-proven, locally advanced unresectable nonmetastatic NSCLC were enrolled. Induction chemotherapy consisted of two cycles (day 1 and day 28) of etoposide (VP16:100 mg/m2, days 1 to 3) and carboplatin (CBDCA:350 mg/m2, day 1). Irradiation starting at day 56, delivered 66 Gy in 2 Gy daily fraction, 5 days a week, along with a daily dose of CBDCA (15 mg/m2) given intravenously 2 to 4 h before radiation. In nonprogressive patients under induction chemotherapy, two additional cycles of VP16-CBDCA were administered 4 weeks after the completion of CRCT. RESULTS: Out of the 40 patients enrolled (38 males, 2 females), 37 (93%) received induction chemotherapy as scheduled, with 38% Grade 3-4 hematological toxicity. Response rate to induction chemotherapy was 11% (4/37). No tumor became resectable. CRCT was delivered to 32 of these 37 patients, with full doses given to 91% of them. Clinical and hematological Grade 3-4 toxicity rates were 21 and 13%, respectively. Additional chemotherapy was delivered in 12 of 26 nonprogressive patients. At final evaluation, performed 3 months after the end of CRCT, 38% of 26 evaluable patients were responders (4 complete and 6 partial), leading to a 25% (10 of 40) overall objective response rate. Of these 10 responders, 8 became responders after CRCT only. Overall, the 1-year local control rate was 28% (11 of 40). The median survival time was 9 months and the 1-year and 2-year overall survival rates were 38 and 15%, respectively. Thirty-six patients died from local progression (25 patients), distant metastasis (9 patients), or pulmonary fibrosis (2 patients). CONCLUSION: Concomitant CRCT with CBDCA is feasible with acceptable induction chemotherapy-related toxicity and a 1-year local control rate of 28%. Response rate to induction chemotherapy was low and better chemotherapy combination should be used to reduce distant failure probability and to improve local response rate before CRCT.

Phase I studies of combined paclitaxel/epirubicin and paclitaxel/epirubicin/cyclophosphamide in patients with metastatic offast cancer: the French experience.

In an attempt to develop new, active, and convenient outpatient combination-chemotherapy regimens for patients with metastatic breast cancer, we performed two phase I studies combining paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus anthracycline for the first-line treatment of metastatic disease, without the use of hematopoietic growth factors. Study I was designed to test the tolerability and antitumor activity of a 3-hour infusion of paclitaxel in combination with an epirubicin intravenous bolus. Study 2 explored a three-drug chemotherapy regimen: a 3-hour paclitaxel infusion with epirubicin and cyclophosphamide. Courses were repeated every 3 weeks. If any dose-limiting events occurred in two or more of six patients in the first course of a given dose level, that dose level was defined as the maximum tolerated dose. Dose-limiting criteria included the following: neutrophils less than 0.25 x 10(9)/L lasting for > or = 5 days, any febrile neutropenia, World Health Organization grade 4 thrombocytopenia, World Health Organization grade > or = 3 nonhematologic toxicity or grade > or = 3 mucositis for more than 5 days, and absence of hematologic recovery at day 35. In both studies, paclitaxel doses were escalated in subsequent groups of three to six patients. For study I, the initial dose level consisted of paclitaxel (110 mg/m2)/epirubicin (50 mg/m2). To date 40 patients have entered the study at eight dose levels. Of the 181 cycles evaluated, grade 3 or 4 neutropenic episodes were observed in 63% of courses, with only five episodes of febrile neutropenia. Grade 2 or 3 neurotoxicity was observed in 43% of patients. Two patients experienced clinical heart failure. The dose-limiting toxicity has not been reached so far. At dose level 7 (paclitaxel [250 mg/m2]/epirubicin [50 mg/m2]), only one patient of six experienced febrile neutropenia. We are currently testing paclitaxel (200 mg/m2)/epirubicin (75 mg/m2). Preliminary evaluation of response documents two complete and 16 partial responses in 37 evaluable patients (48% overall response rate). In study 2, the initial dose level consisted of paclitaxel (150 mg/m2)/epirubicin (50 mg/m2)/cyclophosphamide (500 mg/m2). To date, three dose levels have been investigated in 16 evaluable patients (82 cycles). Grade 3 or 4 neutropenic episodes were observed in 80% of courses, and five episodes were associated with neutropenic fever. Grade 2 neurotoxicity was observed in 28% of patients. The dose-limiting toxicity has not been reached, and we are currently investigating dose level 4 (paclitaxel 225 mg/m2). These trials confirm the tolerability of combined paclitaxel/epirubicin and paclitaxel/epirubicin/cyclophosphamide. The antitumor activity is encouraging.

[Optimization of combined radiotherapy and chemotherapy in treatment of non-small cell lung carcinoma]. / Optimisation de l'association radiothérapie et chimiothérapie dans les carcinomes bronchiques non à petites cellules.

PURPOSE: To report the results of CEBI 140 and 142 trials. These trials were aimed at improving the local control in stage III non-small cell carcinoma with concomitant chemotherapy and radiotherapy in the CEBI 140 trial, and with concomitant chemotherapy and radiotherapy followed by local excision in the CEBI 142 trial. MATERIAL AND METHODS: Thirty-four patients presenting with stage III non-small cell lung carcinoma were included into the CEBI 140 trial from December 1989 to December 1992. Patients were treated with a combination of daily cisplatin (6 mg/m2 per day, 144 mg/m2 in total), vindesine once a week (2.5 mg/m2, 15 mg/m2 in total) and bifractionated radiotherapy (60 Gy/48 fractions/6 weeks) followed by two cycles of cisplatin 120 mg/m2 (at d18 and d45 after completion of radiochemotherapy) and three cycles of vindesine (6 mg/m2 at d24, d31, and d38 after completion of radiochemotherapy). Twenty-eight patients presenting with stage IIIB non-small cell carcinoma-were included into the CEBI 142 trial since January 1993. Patients received a combination of cisplatin (100 mg/m2 at d1 and d24, 200 mg/m2 in total), vinblastine (4 mg/m2 at d1 and d24, 8 mg/m2 in total), 5-fluorouracil in continuous infusion (1,000 mg/m2 from d1 to d3, and from d24 to 26, 6,000 mg/m2 in total) and bifractionated radiotherapy (two series of 21 Gy/14 fractions/9 days, 11 days apart) followed by a new evaluation and surgical excision. RESULTS: In the CEBI 140 trial, all patients received a complete course of radiotherapy, but the dose of cisplatin was decreased in 27% of the cases, and the dose of vindesine in 88%. There were two toxicity-related deaths. Three months after completion of the protocol, there were 50% of complete responders. The overall survival rates at 1, 2 and 3 years were 53, 33, and 11%, respectively, and disease-free survival rates 21 11, and 11%, respectively. In the CEBI 142 trial the immediate tolerance was good. Twenty-one patients (75%) underwent surgical resection. Four tumors could not be resected. Resection was histologically incomplete in one case, and complete in the 16 remaining cases. With a median follow-up of 14 months, ten patients were alive and disease-free. CONCLUSION: Preliminary results of the CEBI 142 trial are encouraging. More patients and longer follow-up are needed for definitive conclusion. It would be of interest to implement a randomized trial comparing the CEBI 142 scheme and classical radiation therapy.

Concurrent cisplatin-vindesine and hyperfractionated thoracic radiotherapy in locally advanced nonsmall cell lung cancer.

PURPOSE: Local failure is a major problem in locally advanced nonsmall cell lung cancer. The main objective of this Phase II trial was to test the feasibility of a combined concurrent radiotherapy and chemotherapy approach in an attempt to improve local control. METHODS AND MATERIALS: From December 1989 to December 1992, 34 patients were included. The treatment schedule consisted of hyperfractionated radiotherapy (60 Gy in 48 fractions and 6 weeks with two daily sessions of 1.25 Gy), cisplatin (6 mg/m2 every day of radiotherapy), and vindesine (2.5 mg/m2 once weekly). After a 3-week rest period, two full cycles of cisplatin (120 mg/m2 on weeks 10 and 14) and vindesine (2.5 mg/m2 on weeks 11, 12, and 13) were given. Treatment evaluation with thoracic computed scan, bronchoscopy, and bronchial biopsies was performed 3 months after completion of radiation therapy. Failure rates were estimated using a competing risk approach. RESULTS: The complete response rate was 50%. Local failure rates at 1 and 3 years were 53 and 56%, respectively. Distant metastases rates at 1 and 3 years were 26.5 and 29%. Overall survival rates at 1, 2, and 3 years were respectively 53, 33, and 12%. Severe esophagitis was observed in three patients (9%). Lethal toxicity was observed in two patients. CONCLUSION: This Phase II trial confirms the feasibility of this type of approach with specific dose reduction and suggests that it may improve local control compared to conventional approaches.

Phase I study of paclitaxel and epirubicin in patients with metastatic breast cancer: a preliminary report on safety.

Attempting to develop a new active, convenient regimen, we initiated a phase I study of paclitaxel (Taxol; Bristol-Myers squibb Company, Princeton, NJ) combined with epirubicin (Farmitalia Carlo Erba, Milan, Italy) in patients with metastatic breast cancer. In addition to standard eligibility criteria, patients with chemotherapy-naive metastasis and at least one measurable lesion had to have left ventricular ejection fractions of at least 50%; the metastatic relapse had to have occurred more than 6 months after adjuvant treatment. Anthracycline-pretreated patients could not have received cumulative doses of more than 300 mg/m2 doxorubicin, 450 mg/m2 epirubicin, or 70 mg/m2 mitoxantrone. An intravenous bolus dose of epirubicin was followed by a 3-hour paclitaxel infusion, with courses repeated every 3 weeks. To date, seven dose levels have been investigated and 31 patients have been treated, 19 of whom had already received anthracyclines. Grades 3 and 4 neutropenia occurred in 37% and 19% of 123 courses, respectively, with five episodes of febrile neutropenia. Grade 2 or 3 neurotoxicity has been observed in 42% of patients and cardiac toxicity in four patients (13%), all of whom had already received anthracyclines. One patient experienced transient myocardial ischemia, one had an asymptomatic decrease in ejection fraction, and two patients had clinical heart failure that required treatment. Dose-limiting toxicity was reached at dose level 5 (paclitaxel 200 mg/m2 plus epirubicin 60 mg/m2), with two of three patients experiencing febrile neutropenia. Reducing the epirubicin dose to 50 mg/m2, however, allowed the paclitaxel dose to be escalated to 250 mg/m2. At this dose level, only one of six patients experienced febrile neutropenia. At a preliminary response evaluation (dose levels 1 to 6), 11 patients (44%) had partial responses, 12 patients (48%) had stable disease, and disease progressed in two patients. We conclude that the combination paclitaxel/epirubicin is safe for patients with metastatic breast cancer and, at this early evaluation, shows promising antitumor activity. Additional patients will be treated at dose level 5 to confirm whether dose-limiting toxicity occurs at this step. Indeed, we took into consideration that dose-limiting toxicity observed at this particular dose level in two of three patients might be due to hazard, since paclitaxel dose escalation up to 250 mg/m2 was further possible in association with 50 mg/m2 epirubicin.

Local relapse and contralateral tumor rates in patients with breast cancer treated with conservative surgery and radiotherapy (Institut Gustave Roussy 1970-1982). IGR Breast Cancer Group.

BACKGROUND: Breast conservation is now established treatment for patients with small breast cancers. The authors reviewed a large series of patients with long term follow-up who underwent conservative treatment. Clinical and pathologic factors were analyzed to identify patients at an increased risk of relapse in the breast (local relapse) or development of a contralateral tumor. METHODS: Seven hundred fifty-seven patients with unilateral invasive breast cancer (T0-2, N0-1, M0) were treated conservatively (wide local excision and radiotherapy) at the Institut Gustave-Roussy between 1970 and 1982. The median follow-up was 9 years. The risk of local relapse or development of a contralateral tumor (as first event) was studied by univariate analysis for the main clinical, pathologic, and treatment factors. Those found to be significant were entered into a Cox proportional regression analysis. RESULTS: Fifty-one patients relapsed in the treated breast (actuarial local relapse rates at 5 and 10 years were 5% and 8%, respectively) and 34 in the contralateral breast (actuarial contralateral tumor rates at 5 and 10 years were 3% and 6%, respectively). Multivariate analysis of the risk factors for local relapse showed that only age younger than 40 years (P < 0.02) or inadequate surgical excisioin (P < 0.02) were significant. No particular risk factors for contralateral tumor development were identified. CONCLUSIONS: Overall, for most patients, the risk of local relapse or of developing a contralateral tumor was low. A small number of young patients with inadequately excised tumors are at higher risk of local relapse, need more meticulous surgery, and may merit higher dose radiotherapy.

Phase I/II study of paclitaxel plus cisplatin as first-line chemotherapy for advanced non-small cell lung cancer: preliminary results.

From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). Nine patients had stage IIIB disease and 23 had stage IV disease. The first four dose levels of paclitaxel were 135, 175, 200, and 225 mg/m2 given with a fixed cisplatin dose of 100 mg/m2; at level 5, paclitaxel 225 mg/m2 was again given, and the cisplatin dose was increased to 120 mg/m2. Cycles were given every 3 weeks. Paclitaxel was administered as a 3-hour infusion followed by cisplatin, with standard premedication and hyperhydration. The maximum tolerated dose for the first cycle was not reached. Grades 3 and 4 neutropenia occurred in 24% and 16% of cycles (two cases with fever), respectively. Grades 2 and 3 peripheral axonal neurotoxicity occurred in two and 16 patients, respectively; the neurotoxicity appeared to be dose dependent and cumulative after a median total paclitaxel dose of 1,300 mg/m2. Of the 29 patients evaluable for efficacy, 11 (38%) had a partial response; efficacy was superior at paclitaxel doses of at least 200 mg/m2, with eight (47%) of 17 evaluable patients responding at these levels. In conclusion, at these doses of paclitaxel and cisplatin, the dose-limiting neurologic toxicity is dose dependent and cumulative after a total paclitaxel dose of approximately 1,300 mg/m2. This combination is highly active, with a total objective response rate of 38% and an objective response rate of 47% at paclitaxel doses of 200 mg/m2 or higher. Further evaluation is warranted.

[Carboplatin and urothelial tumors: review of the literature]. / Le carboplatine et les tumeurs urothéliales: revue de la littérature.

Polychemotherapy appears to increase survival moderately but at a cost of severe toxicity, mainly due to cisplatin. New platinum salts (chiefly carboplatin) have therefore been developed. This review on the use of carboplatin in advanced-stage urothelial tumours was undertaken to find the actual place of carboplatin in the treatment of these tumours, and to describe its best use in polychemotherapy. In 322 patients, carboplatin alone gave 12.9% objective responses (OR), 2.5% complete responses (CR) and 10.4% partial response (PR). Many polychemotherapy protocols were used, most frequently carboplatin/methotrexate/vinblastin. The results were OR: 63%, CR: 19%, PR: 44% among 146 patients. These results confirm the relative efficiency of carboplatin on urothelial tumours, particularly when used in combination. Because of the lack of prospective studies and the wide disparity in the doses and in the dose adjustment, no comparison can be made with cisplatin. Carboplatin has virtually no renal toxicity at the usual doses, and does not require hyperhydratation. The pharmacokinetic behaviour of the two platinum salts is highly different, as carboplatin does not undergo tubular metabolism. The efficiency and tolerance of carboplatin used to be optimised by adapting the dose to the glomerular filtration rate, as was shown for germ cell tumours. In conclusion, these considerations fully warrant further clinical trials of carboplatin.

[Taxol (paclitaxel), first molecule of a new class of cytotoxic agents: taxanes]. / Taxol (paclitaxel), première molécule d'une nouvelle classe d'agents cytotoxiques: les taxanes.

Taxol is the first of the taxanes, a new class of cytotoxic agents whose cellular target is the microtubules network. Taxol induces the polymerisation of the alpha and beta sub-units of the tubulin. This mechanism of action which is different from the vinca-alkaloids explains the main cytotoxic activity of paclitaxel through the formation of abnormal and stable bundles of microtubules. Severe hypersensitivity reactions which were seen in early phase I studies are prevented by an oral corticosteroids and H1 and H2 blockers premedication. Profound neutropenia is frequent but of short duration explaining that infectious manifestations are rare and neutropenia not cumulative. Thrombopenia and anemia are rare. Neurotoxicity is dose related but severe peripheral neuropathy is rare. Conduction abnormalities are mainly asymptomatic bradycardias. In second line ovarian cancer and breast metastatic cancer a noticeable level of activity has been observed, and in lung and head and neck cancer Taxol has proved to be effective.

Neoadjuvant chemotherapy with carboplatin/5-fluorouracil in head and neck cancer.

In a prospective, randomized, multicenter study, neoadjuvant chemotherapy (CT) with carboplatin and 5-fluorouracil (5-FU) followed by locoregional treatment (LRT) was compared with locoregional treatment alone in the treatment of patients with head and neck cancer. This study, which includes 324 patients, was conducted from January 1988 to July 1991. The aim of this study was to evaluate the impact of the carboplatin/5-FU regimen both on the incidence of mutilating surgery and on the survival rate. Chemotherapy consisted of three cycles of carboplatin 400 mg/m2 day 1 and 5-FU 1 g/m2 days 1-5, repeated every 3 weeks. Patients with a complete tumor response then received radiotherapy alone, instead of the treatment planned initially. Three hundred patients were analyzed: 79 had tumors of the oral cavity, 106 oropharyngeal tumors, and 115 pharyngolaryngeal tumors. One hundred fifty patients underwent CT+LRT; 150 patients had LRT alone. Grade 3 and 4 toxicity rates were minimal in the CT+LRT group; toxicity was mainly hematologic (24% neutropenia, 19% thrombocytopenia). There were 3 toxic deaths (2%), 2 due to septicemia and 1 due to cardiac toxicity. One hundred forty-three patients were evaluable for efficacy. The tumor objective response rate was 63% and complete response rate was 31% (35% for oropharyngeal, 34% for pharyngolaryngeal tumors, 22.5% for oral cavity tumors), which led to a 29% decrease in the rate of mutilating surgery. Conservative treatment was performed in 57% of patients in the CT+LRT group vs. 24% in the LRT group (p = 0.001). There was no significant difference between survival curves in the CT+LRT and LRT groups. At 4 years, overall survival rates were 56 and 46%; disease-free survival rates were 33 and 30% in the CT+LRT and the LRT groups, respectively. The survival rates were not significantly different in the two groups. The locoregional recurrence rates were 35% in the CT+LRT arm and 25% in the LRT arm (p = 0.04), with median follow-up of 25 months. The rates of secondary localization and distant metastasis were not significantly different in the two groups.

Results of a randomized clinical trial comparing two radiation schedules in the palliative treatment of brain metastases.

In 216 patients with brain metastases two schedules of brain irradiation were compared in a randomized trial: one course of 18 Gy/3 fractions/3 days versus the same fractionation followed by a second course of radiotherapy with a one-month time interval. The second course was identical to the first one or delivered 25 Gy/10 fractions/14 days. No difference in overall survival, nor in the neurologic response or in the incidence of complications was demonstrated. Two clinical factors appeared to be prognostic of the overall survival: the presence of multiple brain metastases and the presence of extracerebral metastases.

Neoadjuvant combination of carboplatin and 5-FU in head and neck cancer: a randomized study.

A prospective, randomized, multicenter study of patients with oropharyngeal and pharyngolaryngeal tumors compared locoregional treatment alone with neoadjuvant chemotherapy with carboplatin/5-fluorouracil (5-FU) followed by locoregional treatment. The aim of the study was to evaluate the role of chemotherapy on survival and on the need for mutilating surgery. Since 1988, 219 patients (105 with oropharyngeal and 114 with pharyngolaryngeal tumors) have entered the study. All patients randomized to neoadjuvant chemotherapy received three cycles of carboplatin 400 mg/m2 day 1 and 5-FU 1 g/m2/d as a continuous infusion days 1 through 5 every 3 weeks. Neoadjuvant chemotherapy was given to 108 patients. The 268 evaluable courses induced a low rate of grade 3 or 4 toxicity. Four patients (3.6%) died of major complications. The complete response (CR) rate was 31%, which represented a decrease in mutilating surgery of 30%. (Patients with CRs had radiotherapy alone instead of radiosurgical treatment as originally planned.) The objective response rate was 61%. Survival curves for the chemotherapy and chemotherapy-naive groups were not significantly different. The rate of nodal recurrence was significantly higher in the chemotherapy group, however, and chemotherapy did not decrease the rate of second primary tumors or distant metastases. Thus, the justification for neoadjuvant chemotherapy may be a decreased rate of mutilating surgery. These preliminary results are encouraging, but follow-up is as yet too short to allow definite conclusions.

[Combination of chemotherapy (vindesine, lomustine, cisplatin, cyclophosphamide) and thoracic radiotherapy in nonresectable non-small cell bronchial carcinoma: final results of a phase II clinical trial]. / Association chimiothérapie (vindésine, lomustine, cisplatine, cyclophosphamide)--radiothérapie thoracique dans les carcinomes bronchiques non à petites cellules inopérables: résultats définitifs d'un essai phase II.

Seventy-five patients with locally advanced non small cell lung carcinoma were entered in a phase II study combining chemotherapy (vindesine, lomustine, cisplatin and cyclophosphamide) and radical thoracic radiotherapy delivering a total dose of 60-65 Gy. Patients were regularly assessed by radiological and fiberoptic bronchoscopy examinations in order to evaluate local control. An objective response was observed in 22 patients (29%) after initial chemotherapy (2 complete remissions and 20 partial responses). The complete response rate after the combined schedule was 30%. Toxicity of this combination was acceptable. Median survival was 13.5 months. Actuarial risk of developing distant metastases at 3 years was 60%. However, the main cause of failure was local with 80% of uncontrolled or recurrent thoracic tumor in the first 2 years of follow-up. The present study shows that local control remains a major problem in the management of patients with inoperable non metastatic non small cell lung cancer.

Pericarditis and myocardial infarctions after Hodgkin's disease therapy.

From 1971 to 1984, 499 patients with all stages of Hodgkin's disease received mediastinal irradiation at the Institut Gustave-Roussy by 25 MV photons from a linear accelerator. Thirty-five pericarditis (10-year cumulative incidence rate of 9.5%) and 13 myocardial infarctions (MI) (10-year cumulative incidence rate of 3.9%) were observed. In contrast, no cases were diagnosed in a parallel series of 138 Hodgkin's disease patients treated without mediastinal irradiation during the same period of time (p less than 0.005 for pericarditis, p less than 0.05 for MI). By multivariate analysis, the role of total radiation dose given to the mediastinum and that of fraction size were evaluated, adjusting for age, sex, mediastinal involvement, and type of chemotherapy. The pericarditis risk was significantly increased with total dose greater than or equal to 41 Gy (relative risk (RR) = 3.25, p = 0.006) and with dose per fraction greater than or equal to 3.0 Gy (RR = 2.0, p = 0.06). The myocardial infarction risk was not found to be related to total dose nor to fraction size in this series, possibly because of the small number of events.

Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences.

An analysis of the chest recurrences was conducted in 72 consecutive patients with limited small cell lung cancer treated in two successive phase II trials alternating six induction chemotherapy courses and three series of thoracic radiotherapy, followed by maintenance chemotherapy. The total radiation dose was 45 Gy (3 series of 15 Gy) in the first trial, and 55 (20, 20 and 15 Gy) in the second. The effect of the irradiated volume was investigated by comparing the local relapse rates in the group of patients treated by radiation fields encompassing the initial tumor volume to another group in which the initial target volume was not fully covered by radiation fields. The definition of these two groups was performed retrospectively by examination of radiological, fiberoptic bronchoscopy initial findings, technical radiation charts and check films. The local recurrence rate were 33 and 36% in each group (no significant difference). This finding could suggest that tumor shrinkage after chemotherapy might allow the use of "reduced" radiation volumes. However, the limited number of patients does not permit a definite conclusion. The effect of radiation dose was investigated by comparing the local control rates in the two consecutive trials which delivered 45 and 55 Gy, respectively. No difference in long-term local control was found: the addition of 10 Gy in the second trial only seemed to delay the appearance of local recurrences by 6 months. Twenty percent of patients died from a local relapse without evidence of distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternating radiotherapy and chemotherapy in 173 consecutive patients with limited small cell lung carcinoma. GROP and the French Cancer Center's Lung Group.

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

[Combined radiotherapy-chemotherapy in inoperable bronchial carcinoma (small cell carcinoma excluded)]. / Les associations radiothérapie-chimiothérapie dans les carcinomes bronchiques (à l'exclusion des formes à petites cellules) inopérables.

When treated by irradiation alone, non small cell carcinomas of the lung usually experience a very poor outcome. Consequently, more interest is being focussed on radiotherapy and chemotherapy association. The analysis of a randomized trial comparing irradiation alone to a sequential or an alternated combination of radio and chemotherapy did not reveal any clear advantage of the association of both therapies on each technique used alone. It is only when using concurrent irradiation and chemotherapy that some encouraging results are reported. Several non randomized studies used radio and chemotherapy prior to surgery, aiming at increasing the resectability rate. However, the criteria for initial unresectability were not homogeneous and it is not yet clear if such an association really allowed the state of surgical resection to be improved. In the near future it could be worth considering the use of radiosensitizing drugs, synchroneously given with an irradiation delivered with a multiple daily fractionation. This technique would possibly lead to a therapeutic gain, by increasing the local control rate and reducing the metastasis rate, while keeping it to an acceptable level of toxicity.