G. Auclerc

Results of a conservative treatment combining induction (neoadjuvant) and consolidation chemotherapy, hormonotherapy, and external and interstitial irradiation in 98 patients with locally advanced breast cancer (IIIA-IIIB)

Ninety‐eight patients with locally advanced breast cancer (Stage IIIA‐IIIB) were entered into a pilot study combining intensive induction (neoadjuvant) chemotherapy (VTMFAP) with or without hormonochemotherapy, external and interstitial radiotherapy, and consolidation chemotherapy with or without hormonochemotherapy. Tumor regression over 50% was observed in 91% patients after chemotherapy, and complete clinical remission occurred in 100% patients after irradiation. The rate of local relapse is 13%. The 3‐year disease‐free survival is 62% and 3‐year global survival is 77%. Initial chemotherapeutic tumor regression > 75% is the main predictive factor for disease‐free survival.

Ten years of breast preserving management in infiltrative breast cancer : results in 412 patients treated by Neo-Adjuvant chemotherapy and radiation therapy with or without hormonotherapy

The studies that Claude Jacquillat undertook in 1980 in infiltrative breast cancers were inspired by two concepts: breast cancer should be considered in most women as a two components disease, a visible locoregional disease and an invisible systemic disease which constitutes its main danger and its therapeutic priority; since it is not an exclusive locoregional disease, breast preservation must be focused on.

Chemotherapy as a primary treatment of Hodgkin's disease (204 new cases, 1 to 8 years of follow-up)

Two hundred and four untreated patients with Hodgkins disease were given 6 monthly courses of combined therapy with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), followed by monthly vinblastine (protocol H2 65). Fifty of these patients were non-randomly selected to receive complementary or prophylactic irradiation to large fields, either supradiaphragmatic (28 cases), subdiaphragmatic (7 cases) or both of these (15 cases). Similarly, 50 other patients were chosen to receive reinductions with MOPP every three months during the first year, then every 6 months. All treatment was stopped after four years. Splenectomy was not performed routinely but 19 patients underwent splenectomy to define precisely the stage of their disease. Review of lymphography led to reclassification of 37 patients to that of stage II; 91% of whom entered remission, 48% being complete. Of the 109 stage III patients, 52% had a complete remission and 38% a partial remission (P.R.). Of stage IV patients, 40% obtained a C.R. and 26% a P.R. n nRemission curves reached a plateau at the 42nd month: 74 ± 6% for those who entered into C.R. and 56 ± 8% for those with a P.R. (P < 0·03). These patients have been at risk for more than 42 months and 14 have been followed for periods between 5 and 8 years. n nOther factors may have influenced these results: increased age (more than 50 years) greatly decreased the rate of remission (P < 0·001); the more advanced the anatomical stage the worse the prognosis: but paradoxically, histological lymphocytic depletion (L.D.) had a better prognosis than other types (P < 0·02). The clinical signs (A or B) did not influence the duration of the remission, but abnormalities in the parameters of biological activity (b) worsened the prognosis (P < 0·01). Patients who were given complementary radiotherapy had a longer remission (P < 0·001). n nA relapse occurred in 38 patients, but never after the 42nd month. In 21 cases, the relapse occurred in the lymphatic areas which had been involved initially, and in the other 17, there was visceral involvement. In addition, there was a correlation between histological cell type and mode of recurrence: local recurrences occurring predominantly in lymphocytic predominance (L.P.), nodular sclerosis (N.S.) and widespread relapses occurring in mixed cellularity (M.C.) and (L.D.). n nThe overall survival reached a plateau at the 48th month of 72 ± 10%, this being influenced by the same factors as the remission. However, the beneficial effects of complementary irradiation (P < 0·05) and reinductions (P < 0·05) were certain. n nThus the value of polychemotherapy is confirmed. Prognosis in Hodgkins disease may be related directly to the administration of polychemotherapy before the radiotherapy. These two modalities must be used in flexible association dependent on the staging which must include all the parameters.

955 A phase I study of concomitant CPT-11 (C) and 5FU (F) combination: Preliminary results

CPT-11, a DNA topoisomerase I inhibitor has been confirmed to demonstrate an anti-tumor effect specially against colorectal cancer (CRC). In order to define the best schedule combining the most two active agents in CRC, we initiated in June 94 a phase I study at the starting dose (level 1) of C 200xa0mg/m2 (over 30xa0minutes) and F (500xa0mg/m2 on day 1 to 5 by IV bolus administration). To find a sequence-dependent toxicity, C was given at day 0 on cycle 1 (CF) and at day 6 on cycle 2 (FC), then the better tolerated cycle was continued. Escalation schedule initially projected for C was 200, 230, 260, 300, 350, 400, 450 and 500xa0mg/m2. A death occurred at the level 1 (fatal dyspnea in a patient with a bulky mediastinal involvement), probably not related to the treatment, but we decided to reduce 5FU to 375xa0mg/m2/day. Characteristics of the 16 patients entered in the study are following: median age: 57 years (range: 40–70), sex: 12 males, 4 females, PS: 0: 9, 1: 7; all patients had solid tumors refractory to previous treatment (colorectal: 12, oesophagus: 2, lung: 1, pancreas: 1). Level CPT-11/5FU No. pts No. Cycles Diarrhea gr.III/IV Neutropenia gr III/IV 1 200/500 2 2 1/0 1/1 2 200/375 8 34 3/1 0/0 3 230/375 6 12/0 0/0 3/0 5 hospitalizations (1 at level 3) occurred (2 for IV fluid administration) and alopecia was reported in 1 patient (level 3). Further escalation is warranted to determine the maximal tolerated dose. A pharmacodynamic study is underway to investigate potential interactions between C, F and SN38 according to the schedule administrations.

Neo-Adjuvant chemotherapy in breast cancer Study of 477 evaluable patients with primary breast cancers treated between 1980 and 1992

Neo-Adjuvant chemotherapy in breast cancer means that chemotherapy is used as the first therapeutic tool and that the locoregional treatment is considered as an adjuvant. The term has been contested and others were proposed, but induction treatment is too specific for the first chemotherapy combination used in leukemia to achieve complete remission. Primary treatment does not encompass the consolidation phase which belongs to our strategy so that even if it is not quite satisfactory we keep the term Neo-Adjuvant which has been coined in the seventies by E. Frei for head and neck cancers.

Results of Cisplatin (CDDP)/Etoposide (VP16)/5-FU and alternatively Adriamycin or Mitomycin C (PEFAM) combination in primary resistant breast cancer and in heavily pre-treated metastatic breast cancer

In spite of the activity of chemotherapeutic agents, metastatic breast cancer remains an incurable disease.