Tumorectomy and radiotherapy in early breast cancer: a report on 392 patients.

This study includes 392 patients (231 Stage I and 161 Stage II) treated by tumorectomy followed by radiotherapy. The overall actuarial survival for all the patients is 86.5% at 5 years and 78% at 10 years. The 5-year NED survival is 70.2%. The survival rates are depending on the loco-regional extension: Stage I: 92% survival at 5 years and 84% at 10 years; Stage II: 82% survival at 5 years and 75% at 10 years. The percentage of local recurrences were 13% for all stages (10.6% for Stage I, 16% for Stage II), of lymph node recurrences: 1.5% for all stages, 1.3% for Stage I, 2% for Stage II, of distant metastases: 11.2% for all stages, 8% for Stage I and 16% for Stage II. The loco-regional control rates were analyzed according to the TNM classification and discussed and compared to several literature data. The breast preservation rates were at 5 years 85% for Stage I and 80.9% for Stage II. Cosmetic results are judged as good in 80% by doctors and in 90% by patients themselves with very low complication rates.

Exclusive radical radiation therapy in breast carcinoma.

We present the results of 186 breast cancer patients treated initially for locoregional disease by radiotherapy alone, combining cobalt therapy with external electron beam or interstitial iridium implants. According to the TNM classification, the patients were distributed as follows: 3 T1N0, 2 T1N1, 33 T2N0, 36 T2N1, 16 T3N0, 26 T3N1, 6 T3N2, 14 T4N0, 29 T4N1, 9 T4N2 and 12 T4N3. The 5- and 10-year survival rates (52.7% and 36.5%, respectively, for all patients) were directly correlated with the size and location of the breast tumor, and the extent of lymph node involvement. Locoregional recurrence was observed in 39.8% of the cases, metastasis alone in 26.8% of the cases, and a combination of local recurrence and distant metastasis in 14.5% of the cases. The local recurrences and metastases were directly correlated with the extent of locoregional involvement. Late complications and sequelae were mostly minor and occurred in less than 25% of the cases; severe sequelae occurred in no more than 2% of the cases. They depended on the initial tumor volume and the tumor dose. Our results, along with those in the literature, indicate that radiotherapy administered alone is a valid therapeutic option in breast cancer.

Follow-up results from a randomized trial for T3 and T4 breast cancer patients: previous BCG immunotherapy improves response to chemotherapy in the relapse patient.

Following locoregional treatment, patients were randomized into three groups: The first groups received no complementary treatment; the second group received adjuvant chemotherapy (vincristine, cyclophosphamide, and 5-fluorouracil once a month for 12 months); and the third group was treated by immunotherapy (150 mg BCG once a week for 1 year). Sixty-two of the 82 patients studied were menopausal. No significant difference was observed between the three groups. All patients were followed-up for at least 18 months. The disease-free interval difference between the chemotherapy group and the control and immunotherapy groups is not significant. But it should be noted that only 21.8% of the control group did not relapse compared to 57% in the chemotherapy group. BCG immunotherapy in such patients must be considered ineffective. However, our results suggest that patients first treated with BCG respond better to chemotherapy than patients not receiving any previous therapy.

[Rubidazone (22 050 RP): clinical study. Phase II trial in solid tumors and lymphomas (author's transl)]. / Rubidazone (22050 RP): étude clinique. Essai de phase II dans les tumeurs solides et les lymphomes.

Rubidazone is a semisynthetic antibiomitotic close to daunorubicin and doxorubicin. Fifty two patients with various advanced cancers received rubidazone intravenously at the initial unitary dose of 200 mg/m2 in a single injection at three week intervals; this base line dosage had been adapted in function of leuko-platelet variations observed between the injections. An objective improvement was noted in 18 patients out of 51 evaluable patients (34% of the cases), 6 times the regression of tumoral volume was greater than 50 per cent but not complete (3 breast adenocarcinomas and 3 lymphomas). Manifestations of intolerance-toxicity were minor on the haematologic side (32%); however, they were relatively frequent from the digestive (63%) and general (82%) point of view; symptoms of cardiac disturbances (21%), responsible for the discontinuation of the chemotherapy, necessitate careful attention in the management of the treatment. The comparison of the results of this trial with those obtained by trials using other drugs belonging to the same chemical family don't show, for solid tumors, any difference in efficacy between rubidazone, daunorubicin or duborimycin; however, the difference is very striking with doxorubicin which showed more efficacy (6.5% as 29% of regression greater than 50%). Owing to the conditions of admission and the very strict criteria of analysis in this study, it would seem useful to go into details regarding the interest of rubidazone in lymphomas (only one failure has been recorded out of 6 treated cases).

[Chemotherapy in cervical cancer. Assessment of 267 palliative treatments and current trends (author's transl)]. / La chimiothérapie des cancers du col utérin. Bilan de 267 traitements palliatifs et orientations actuelles.

Over the last 10 years 267 treatments with cervical cancer have been treated with chemotherapy in 4 anticancer centers. The analysis of these results shows: 1) 9 per cent of the treatments were discontinued because of clinical and hematological intolerance reactions; these intolerance reactions were responsible for 1 per cent of the therapeutic deaths; 2) an effect on the functional symptoms in 52 per cent of the patients with multiple drug regimens; 3) an objective global response in 18 per cent of the patients treated with single drug therapy (3 regressions greater than 50% out of 6 cases treated with cis-platinum) and in 22 per cent of the patients treated with various associations. Comparison of these results to recent data in the literature confirms: 1) the hope of improving objective results by developing more rational protocols of association, since, for the moment more active drugs are not available; 2) a much more marked chemotherapeutic action on lesions which have not been previously irradiated (statistically significant differences in response). Chemoresistance in cervical cancers may not be as frequent or as insurmountable as generally believed. The role of chemotherapy may be visualized from: 1) the palliative point of view, for efficacy while reducing toxicity); 2) induction sequence in curative treatment programs for advanced local forms with unfavorable prognosis (logical and attractive orientation of therapeutic studies); 3) the point of view of adjuvant treatment which remains to be defined. Rigorous studies are required to assess whether chemotherapy can give eventual long term improvement in high risk cervical cancers.

[Preoperative irradiation in the treatment of rectal carcinoma: study of results of 116 cases at five years (author's transl)]. / L'irradiation préopératoire du cancer. Résultats à 5 ans de 116 cas.

Pilot study of combined radiosurgical treatment of carcinoma of the rectum. 116 patients underwent surgical excision of a carcinoma of the rectum after concentrated preoperative irradiation giving 40 grays in 18 sessions over the pelvic tumour volume. The operation in 79 cases consisted of abdomino-perineal excision and in 37 cases of anterior resection. The node involvement noticed on the resected volume is of 16,4 per cent. The operative mortality is of 7,7 per cent and the complications due to radiotherapy itself mainly a delay in cicatrisation. Survival rate at five years is of 60 per cent. Preoperative irradiation seems to be realy a benefit in the treatment of rectal carcinoma.

[Randomized trial of vincristin-methotrexate-bleomycin and cis-platin or detorubicin for advanced head and neck cancer (author's transl)]. / Etude randomisée d'une association de vincristine-méthrotréxate-bléomycine et cis-plastine ou détorubicine dans les cancers avancés des voies aérodigestives supérierures et de l'oesophage.

In a randomized multicenter trial, 151 patients, with advanced epidermoid carcinoma of the head, neck and oesophagus, were treated with an association of vincristin, methotrexate, bleomycin and cis-platin (group I) or detorubicin (group II). Prognostic factors were equally distributed for the both groups. Partial or complete responses were obtained in 22 patients of group I (29 p. cent) and 9 in group II (12 p. cent, p less than 0.05). Objective response rates were higher in untreated patients or those in good condition but the difference was not statistically significant. Five probably treatment induced deaths (3 p. cent) were observed. Treatment was stopped in 2 patients (15 p. cent) for haematological, general or digestive toxicity. This trial confirms the efficacy of vincristin, methotrexate, bleomycin and cis-platin for advanced head and neck carcinomas.

[A randomized study comparing cisplatin alone or combined in the palliative treatment of carcinoma of the head and neck. Analysis of a series of 209 patients]. / Etude randomisée comparant le cisplatine seul ou associé dans le traitement palliatif de carcinomes des voies aéro-digestives supérieures. Analyse d'une série de 209 patients.

Two hundred and nine patients, with locoregional or metastatic recurrences of head and neck epidermoid carcinoma, were randomized to receive a palliative chemotherapy. The chemotherapy regimens were delivered every 3 weeks, and consisted in (1) cisplatin, 80 mg/m2 given alone (CDDP regimen), or (2) in combination with vincristine, 1 mg, methotrexate 10 mg/m2 d 1, 2, 3, and bleomycin 10 mg/m2, d 1, 2 and 3 (1040 regimen). Short-term results were better for patients treated by the 1040 regimen, with a 30% response rate (including 4 complete responses) vs 15% with the CDDP regimen (P = 0.01). A superiority of combination chemotherapy was found for all tumoral sites, but was particularly significant for pulmonary and cutaneous metastases, in previously un irradiated areas (P = 0.001). Tolerance was significantly better with the CDDP regimen (P = 0.001); severe side effects, affecting mainly general status, digestive tract and bone marrow were encountered in 5% of the patients in the CDDP group, vs 21% in the 1040 group, with one death related to pancytopenia. The median duration of remissions was not statistically different in the 2 groups, as well as the 2 years overall survival. Among responders, the survival was slightly better in those treated with CDDP alone; moreover, the quality of long term results was found highly correlated with a good initial general status, and with low levels of side effects. Those results confirm recent data of the literature, and lead to the following conclusions: (1) combination chemotherapy with CDDP give a better response rate than CDDP alone, (2) response rate doesn't influence overall duration of survival, (3) tolerance to treatment is crucial to preserve quality of life, and thus, (4) palliative chemotherapy in head and neck cancer should be efficient but also as short of intensity as possible.

[Cancer of the rectum: preoperative radiotherapy (344 cases)]. / Cancers du rectum: radiothérapie pré-opératoire (344 cas).

Radiation therapy prescribed as an adjuvant to surgery is an effective treatment of many cancers but has not been universally accepted for treatment of rectal cancer. Since 1969, preoperative radiation therapy of rectal carcinoma has been proposed in a curative intent, both at Centre Paul Lamarque in Montpellier and at Centre Claudius Regaud in Toulouse, France. Megavoltage radiotherapy was used in all patients and doses ranges from 35 to 40 Gy during 2.5 to 3 weeks. Among the 344 patients treated between 1969 and 1981, the ratio of abdominoperineal excision to anterior resection was 239/105, the percentage of pelvic recurrence was 7,8 per cent, and the 5-year survival rate, including postoperative mortality (5.2%) was 78 per cent in the Centre Claudius Regaud series and 64 per cent in the Centre Paul Lamarque series. The 10-year survival rate was 50 per cent. There was no evidence of an increased morbidity following irradiation. Pathologic staging showed no residual tumour in the excised specimen in 5.2 per cent of the cases. The number of Dukes'C cases was smaller than according to the clinical pre-treatment assessment of the tumours (16%). Ultrasonography of the liver and plasmatic CEA determination avoid irradiation of metastatic patients. Further development of this curative approach should include a postoperative boost of 25 Gy for patients who are at high risk for local failure in the pelvis, and an adjuvant chemotherapy for Dukes'C patients.

[Anticancerous chemotherapy trial with duborimycin. Analysis of 151 cases]. / Essai de chimiothérapie anticancéreuse par la duborimycine. Analyse de 151 observations

Duborimycin is a new antimitotic agent approaching danorubicin and adriamycin in activity which has been tried on 151 patients suffering from cancer of different types, is an advanced local/regional stage and/or metastatic disease. It was administered intravenously every fortnight in a mean unit dose of 400 mg, and the duration of the treatment ranged from 2 to 52 weeks. Objective improvement was registered in 56 patients of the 135 cases in whcih the results were assessed (around 41.4% of cases). In 4 cases the regression of tumour volume was greater than 50% (one of these cases was in melanoma, the other a sarcoma) and in 2 cases regression was complete (a squamous cell carcinoma and an embryonal testicular tumour). The subjective effects were appreciable in 53 of the 115 cases which could be studied (46%) and above all in the refractory pain of bony secondaries from breast cancer (a favourable response in 78% of cases). Manifestations of intolerance/toxicity were of a minor nature on the haematologic side, that cardiologic ones relatively frequent (18% of treated cases) and occasionally serious (2 cases of asystole). Great care is therefore necessary in supervision of the treatment. However, the first results obtained by this line of approach, notably in chemo-resistant forms of tumour such as melanoma and sarcomas, utilizing the very strict criteria in one analysis encourage further study of duborimycin in cases of this sort (preferably in association and in accordance with protocols of comparative trials) so that its place in cancer chemotherapy may be more precisely defined.

[Chemotherapy of soft tissues sarcomas. Summary of a decade and current trends]. / La chimiothérapie des sarcomes des tissus mous. Bilan d'une décennie et orientations actuelles

The results of palliative chemotherapy applied to 123 patients with disseminated soft tissue sarcomas are reviewed with the recent literature data. With the exception of embryonal rhabdomyosarcomas of children, which are considered separately, the response of these tumors to chemotherapy is poor but not negligible. The association of several active drugs should permit substantial progress, especially in the initial stage of local treatment, when the number of disseminated cells is still reduced. A follow-up of controlled clinical studies must specify the modalities of multidisciplinary treatment in an effort to reduce regional recurrence or metastasis.

[Polychemotherapy of advanced breast cancer. Triple combination with doxorubicin. Analysis of 209 observation]. / Polychimiothérapie des cancers mammaires en phase avancée. Association ternaire avec doxorubicine. Analyse de 209 observations.

Two hundred and nine patients with breast cancer in an advanced stage were treated according to a chemotherapeutic regimen associating doxorubicin, vincristine and methotrexate, administered in courses of 5 days every three weeks. This analysis deals only with the short range results; they confirm those of a previous randomized study. A global objective response was obtained in 187 cases (89%) and a measurable regression of the lesions in 150 cases (71%); in these later cases 90 (43%) had a regression of more than 50 per cent. The most striking effects, often rapidly observed, involve sites which are not generally sensitive: liver (40%), pleura (24%) and bone (only 6%, but 8 times out of 10 a definite action on the pain syndrome). Side effects were, on the whole, acceptable (only one severe hematologic complication); however, the risk of myocardiac toxocity due to the accumulation of doxorubicin limits the utilization of this association. It thus needs to be relayed by other drug regimens which are included in a program of long term action, but has interesting characteristics as induction chemotherapy.

[Cancer of the prostate: results of radiotherapy. Multicenter study]. / Cancer de la prostate: résultats de la radiothérapie. Etude intercentres.

From 1975 to 1982, 597 patients with localized prostatic adenocarcinoma were treated using external beam irradiation in one of 6 cooperating centers. The mean patient age was 67 years. The 5 and 10 years actuarial survivals (including all causes of death) were 70% and 40% respectively. The adjusted survival rates become 86% at 5 years and 61% at 10 years when only death due to cancer is taken into consideration. Despite the fact that patients with stage A1 and A2 disease show different patterns of lymphatic spread, the actuarial and adjusted 8 years survivals were identical for both staging groups, in this study, 57% and 90%, respectively. It is significant that the majority of patients in both group A1 and in group A2 received irradiation to the pelvic lymph nodes as well as the prostate. Patients with stage B1 disease showed a 7 years actuarial survival of 53% and an 82% survival adjusted for death due to cancer only. Patients in both group B2 and group C, showed an identical 10 year actuarial survival rate of 49%. However, without CT scanning, it is difficult to differentiate between these 2 staging groups. Patients with stage C2 disease showed 10 years actuarial and adjusted survival rates of 20% and 40% respectively. The local recurrence rate after primary radiation therapy did not exceed 11% in any patient group. These data demonstrate, once again, that the dogma pertaining to the radioresistance of prostatic cancer is outdated.

[Pre-operative irradiation in the treatment of cancers of thoracic esophagus]. / L'irradiation pré-opératoire dans le traitement des cancers de l'oesophage thoracique

The authors analyse an homogeneous series (2 operators) of 650 patients operated on for thoracic oesophageal carcinoma, of which 185 were submitted to pre-operative irradiation with cobalt. Irradiation led to a definite increase in the resectability rate 74 p. 100 as against 62 p. 100. There was an increase in the mid-term survival rate, especially an increase of 5 p. 100 at 2 years, 8 p. 100 at 3 years, 6 p. 100 at 4 years; The 5 survival rate was little modified. It was 12 p. 100 for 290 cases, resection alone, and 15 p. 100 for 137 resections after irradiation.

Tumorectomy and radiation therapy in early breast cancer: a report on 392 patients.

Three hundred ninety-two breast cancer patients (231 with stage I and 161 with stage II disease) were treated with tumorectomy followed by radiation therapy. The overall actuarial survival rate was 86.5% at 5 years and 78.0% at 10 years. The 5-year disease-free survival rate was 70.2%. Survival rates depended on locoregional tumor extension. Patients with stage I tumors had a survival rate of 92.0% at 5 years and 84.0% at 10 years; patients with stage II tumors had a survival rate of 82.0% at 5 years and 75.0% at 10 years. The percentage of patients with local recurrences was 13.0% for all patients (10.8% for stage I and 16.1% for stage II patients). The percentage of patients with lymph node recurrences was 1.5% for all patients (1.3% for stage I and 1.9% for stage II patients). The percentage of patients with distant metastases was 11.2% for all patients (7.8% for stage I and 16.1% for stage II patients). Locoregional control rates compared favorably with those in the literature. Breast preservation rates at 5 years were 85.0% for stage I and 80.9% for stage II patients. Cosmetic results were judged good by physicians in 80% of patients and by 90% of the patients themselves. Complication rates were very low.

[Radiological and surgical treatment of cancer of the thoracic oesophagus: a report on 143 cases (author's transl)]. / Le traitement radio-chirurgical du cancer de l'oesophage thoracique. A propos de 143 cas.

It would appear that pre-operative radiotherapy early in the treatment of oesophageal cancer has avoided in many cases (especially those in an advanced stage), the appearance of local recurrences, which cause death very rapidly during the first year in those patients having surgical treatment only. This treatment, however, which is only localized to the mediastinum, has not prevented the appearance of metastases at a later date. It is obvious, therefore, that though we have improved local prognosis by localized and regional treatment, and the association of radiotherapy and surgery, we have not been able to act on the residual cancerous disease, and something else is needed. This "something else" must be chemotherapy, but at the present time we do not know which product, at which dose, and at which moment, this chemotherapy should be applied to be most effective.

[Chemotherapy in advanced malignant melanoma. Results of a controlled trial comparing a combination of dacarbazine (DTIC) and detorubicin with dacarbazine alone]. / Chimiothérapie des mélanomes malins évolués. Résultats d'un essai contrôlé comparant l'association de détorubicine et de dacarbazine (DTIC) à la dacarbazine seule.

51 patients with malignant melanomas who had not previously received chemotherapy were studied in a phase III trial. They were all advanced cases, either in relapse or showing metastatic spread and with one or several measurable tumor sites. They were judged to be too advanced for surgery or radiotherapy. They were split at random into two groups. Both groups received DTIC (250 mg/m2, IV, over 4 days every three weeks) and one group received detorubicin (120 mg/m2, IV every three weeks) as well. Detorubicin is a new anthracyclin drug which has shown promise in the treatment of these tumors in a previous trial. The combination of the two drugs produced better results than dacarbazine alone. Eight 50% regressions were obtained out of 22 cases studied (36%) with the combination, as opposed to 4 out of 26 (15%) with the single drug. The average length of response was also longer for the combination, i.e. 6 months opposed to 5 for the single drug. The differences were not, however, statistically significant (X2 = 2.09). Toxic reactions were also more frequent with the combination therapy (65%) than with DTIC alone (40%) (X2 = 0.42), as well as more serious because of the myocardial toxicity of the anthracyclin drug. This trial showed that a combination of dacarbazine with detorubicin improves the therapeutic outcome. Whether this represents a real benefit will need statistical confirmation from trials of combinations using other anthracyclins.