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Contrary to the treatment of leukemia and lymphoma which is clearly defined, for most solid tumors the place, the type and the intensity of treatments remain under discussion. Experimental results are available to prove the benefit of various drug combinations in which doses, routes of treatment, schedule and number of cycles are carefully evaluated. However considering the difficulties in testing all the combinations which are possible and the lack of trust in the predictive value of experimental studies, it is generally according to clinical results that escalation or reduction of chemotherapy are decided, At the present time and for many solid tumors, escalation is predominating due to the low effectiveness of the current drugs we have at our disposal. It is only in the case of curable solid tumors (for example: carcinoma of the testis, choriocarcinoma) that a reduction phase is possible and this behaviour is justified in avoiding the iatrogenic effects of chemotherapy. Many examples of escalation and reduction are given in clinical cancer chemotherapy.

Evolution in concepts relative to administration of cytotoxic drugs has reinforced interest in the use of continuous infusion therapy, a method providing a twofold increase in upper respiratory and digestive tract cancer response. A new method, developed by the authors since early 1985 allows the use of chemotherapy over 5 to 10 days in the patient's home. Preliminary results show an increase in efficacy of the therapy, and a marked improvement in the patient's comfort, suggesting that the indications for this new method should be enlarged.

This study was made on 98 patients with breast cancer, whose first discovered metastasis was to the bone, a mean of 2.8 years following the initial diagnosis. It is most often a lytic lesion, and the majority of patients have more than two areas on bone scintiscan. About half of the patients received palliative radiotherapy; 16 had to undergo surgery for or to prevent pathologic fractures. All patients underwent chemotherapy with vincristine or vinblastine, methotrexate or cyclophosphamide, 5-fluorouracil and, in 37 cases, the addition of adriamycin. Half of the patients also received tamoxifen. Present studies show a mean survival of 31 months with 24% survival at five years. Age, the interval to the discovery of the first metastasis, the use of additional chemotherapy following surgery for the breast lesion, the sedimentation rate, and the number of bony metastases do not play any prognostic role. However, the prognosis is significantly improved by adding tamoxifen, and even more so by adding adriamycin to the chemotherapeutic protocol since mean survival improves from 26 to 52 months. The reduced incidence of bony metastases with chemotherapy following surgery had led some authors to believe that prevention is the best method of treating bony metastases from breast cancer.

A series of 185 squamous cell carcinomas of the head and neck was retrospectively analyzed. Induction chemotherapy was systematically administered. The overall tumour response rate was 38 per cent, and 39 tumours (22.4 per cent) became resectable after chemotherapy. The survival of complete responders was statistically higher than that of non or partial responders. Complete responders treated either by radiation therapy or surgery had similar survivals. Surgery improved the prognosis and reduced the rate of local and regional failures in non responders, including poor responders (less than 50 per cent).

In a retrospective study of 1 094 patients treated for Hodgkin's disease between 1963 and 1976, we have observed 65 malignant complications including 28 granulosis acute leukemias and 37 solid tumors. The actuarial 10 year risk of developing acute leukemia is 4.7 per cent; and 5.4 per cent for solid tumors. These figures vary according to the medications received. They are more important in the case of polychemotherapy, particularly for acute leukemia, thus confirming the specific role of alkyl agents. While the course of solid tumors does not seem to differ from that of identical primitive tumors; on the other hand, induced leukemia seems to have a more perjorative prognosis than spontaneous leukemia and they are often announced by cytopenia. The overall risk of developing secondary cancer is multiplied by 2.4 compared to the normal population; that of developing acute leukemia is multiplied by 9.3. In order to reduce this risk, active non alkyl agents of limited duration must be advocated. Irradiation fields must also be reduced.

The diagnosis of myelofibrosis depends on three fundamental criteria. Myeloid metaplasia of the liver and spleen, absence of Philadelphia chromosome and a variable degree of myelofibrosis. It is thus necessary to have available bone and marrow biopsies to make the diagnosis. The analysis of elementary lesions, together with their grouping, was at the origin of various pathological classifications, including those of Hickling and Jacquillat, Chom and Ripault. The latter, adopted by most authors, distinguishes three histological types, depending on the degree of myelofibrosis and bony sclerosis. They are usually considered as successive stages of the disease.

Diaziquone, a new alkylating agent which crosses the blood brain barrier, has shown a 20% response rate in phase II studies in heavily pretreated patients. We have treated 23 patients at our institution as part of a multicentric phase II European trial of diaziquone. All had histologically proven malignant glioma unequivocally progressing on CT scan. Prior therapy had consisted of surgical excision (13 patients), cobalt radiotherapy to CNS (13 patients), and chemotherapy with nitrosourea derivatives (11 patients). Six patients had no prior therapy. Median age was 42 years (range 22-69) and performance status was 3+ or better. They were treated with monthly courses of diaziquone 5.5 mg/m2 I.V. (10 min.) X 5 days. Dosage adjustments were made according to leucocyte and platelet nadirs. Thrombocytopenia was the dose limiting toxicity. Very mild gastrointestinal toxicity was observed. One patient developed hemolytic anemia. One complete response (clinical and CT scan), 7 partial clinical responses (3: greater than 50%, 4: 25-50%), and 1 disease stabilization (less than 25%) were documented. The longest response has now lasted over 26 months. These preliminary results show that chemotherapy with diaziquone can achieve a response rate as high as 35% in malignant glioma even in patients previously treated with a chemotherapy regimen including a nitrosourea (four of the seven objective responses were seen in such patients). Diaziquone is well tolerated and deserves further study in the management of malignant glioma.

A case of malignant phaeochromocytoma is reported. The primary tumour was removed in 1970. Metastases were diagnosed in 1979 and management of the condition included antihypertensive treatment with alphamethylparatyrosine, antitumoral chemotherapy and surgical reduction of secreting tissue. In these rare tumours malignancy can only be confirmed by metastases, i.e. presence of chromaffin cells in loci where they are not usually found. Histology is of little value. High levels of catecholamine precursors or their metabolites in the urine may be a sign of malignancy, but some asymptomatic tumours are only revealed by metastases. Computerized tomography and radioisotope scanning with I131 metaiodobenzylguanidine are the best available methods to locate the lesions. In view of the small number of cases and of the unpredictable course (sometimes spread over many years) of malignant phaeochromocytomas, the effectiveness of treatments with alphamethylparatyrosine, chemotherapy and radiotherapy is difficult to evaluate.

Twenty-two patients with metastatic malignant melanoma received either 36 X 10(6) U (15 patients) or 18 X 10(6) U (7 patients) of human recombinant interferon alpha-2-A daily for 3 months by the intramuscular route, with progressive increase of dosage. This was followed in responders by a maintenance treatment consisting of 3 intramuscular injections per week in the same doses as those received at the end of the induction treatment. Out of 18 patients assessable for effectiveness, 1 had complete remission (7 months +) and 3 had partial response (52,61 and 82 days respectively), an overall improvement rate of 22%. The main side-effects observed were: pseudoinfluenza syndrome (100%), fatigue (100%), somnolence (95%), anorexia (90%) and haematological disorders. Dosage reduction was necessary in 13 of the 15 patients receiving 36 MU. This study shows that human recombinant interferon alpha-2-A has antitumoral activity in metastatic malignant melanoma. Other studies, notably with therapeutic combinations, are needed to determine the optimal dosage regimen of the drug and to increase its effectiveness.

The distinctive features and prognosis of Hodgkin's disease with initial bone marrow involvement were studied in 53 patients. This form is characterized by clinical and biological signs of rapid evolution, diffuse lymphoid tissue involvement with enlarged liver and spleen, increased lymphocyte depletion and pancytopenia--the last named being rare in other forms. Sternberg cells were found in 80% of bone marrow biopsies, often associated which fibrosis, which always disappeared during remissions. Remission was obtained with multiple chemotherapy (chiefly MOPP) in 82% of the patients and was complet in 44%. Blood toxicity was severe in cases with myelofibrosis. Relapses occurred in 14 out of 39 patients and were either local and responsive to radiotherapy or diffuse and invariably lethal. They usually took place in those lymph nodes which were most affected initially. Additional radiotherapy and courses of MOPP reduce the risk of relapse. The long-term prognosis was similar to that of other visceral forms, with a survival rate leveling off at 83% after 6 years in patients in complete remission.

A multicentre clinical trial was organized by the International Antimicrobial Therapy Project Groups of the European Organisation for Research on the Treatment of Cancer (E.O.R.T.C.) to compare the effectiveness of three combinations of antibiotics (azlocillin + amikacin; cefotaxime + amikacin and ticarcillin + amikacin) in patients with malignant leukopenic and febrile diseases (polymorphonuclears less than 1000/mm3; temperature greater than 38.5 degrees C). Some 800 patients from 20 centres entered the study. Preliminary results in 421 assessable patients showed a 62% positive response rate. The response rate in patients with bacteraemia was twice as high in the azlocillin group than in the other groups, the difference being significant at p less than 0.02. This difference does not seem to be due to a distribution bias, since the responsible micro-organisms, the severity of granulopenia, the incidence of bacterial-resistant strains, etc., were similar in all three groups. Similarly, the death rate was 12% in the azlocillin-amikacin group as against 15% and 17% respectively in the other groups. It would appear from this trial that the azlocillin-aminoglycoside treatment is superior to the other antibiotic combinations tested in this category of patients.

Tumoral responses to 3 courses of induction chemotherapy were investigated in 176 patients with squamous cell carcinomas of the head and neck previously untreated. The number of responses increased with the number of courses. Thus, out of 79 patients with a more than 50% response after the 3 courses, almost one third had no response after the first course, and 98.8% had a less than 50% response after the second course. In consequence, it may be stated that a 3rd and perhaps a 4th course is justified in patients who responded after 2 courses. There seems to be a poor correlation in responders between clinical and histological results: 68.5% of patients with complete response still had a tumour on the excised tissue. No correlation was found between the influence of T in the TNM clinical classification and that of squamous cell differentiation on the one hand and the macroscopic character of the tumour during response on the other hand.

In acute lymphoblastic leukaemia the combination prednisone-vincristine induces more than 85% complete remissions. L-asparaginase which was used in complete remissions, seemed to increase their duration. Actually the best maintenance treatment consists in the combination of 6-mercaptopurine and methotrexate interrupted by reinductions. In other respects C.N.S. prophylaxis with intrathecal methotrexate and craniospinal irradiation is necessary. The well-known prognostic factors are: age, leucocytosis, tumoral syndrome, and cytological type: 216 cases of long remission have been observed. One group of these patients was treated by old methods: this represents 0.8 to 1% of the material, while 20% were treated by recent protocols with reinductions (20%).

We have developed a simple, rapid, and sensitive enzyme-linked immunoadsorbent assay (ELISA) to measure soluble cell-free human Fc gamma receptor (Fc gamma R) in serum. This assay is based on the use of two monoclonal antibodies directed against different epitopes expressed on the same low avidity human Fc gamma R (CD16), which is present on polymorphonuclear leukocytes, macrophages and NK cells. This sandwich ELISA, which can measure 2 nM concentration of Fc gamma R, has enabled us to demonstrate the presence and to measure the level of soluble cell-free human Fc gamma R (CfH-Fc gamma R) in normal human serum.

A total of 1200 children were treated for leukemia between 1958 and 1971, and 100 of these cases have had an uninterrupted remission for more than seven years: 10 children who relapsed at an early stage have had no further relapses; 93 are alive and in remission after discontinuation of treatment for between 1 and 12 years. Five of the children relapsed and four of these are in remission again. Two children died, one from a hepatocarcinoma and the other after cardiac failure of late onset. A study of these children showed that: 1 - growth rate was normal, 2 - puberty occurred at a normal age, and procreation was possible as 10 children were born from parents who had recovered after having leukemia, 3 - school-work and subsequent social and occupational behaviour were satisfactory, 4 - late psychological repercussions were absent or mild. Long-term prognosis appears to be good, and no other blood disorder has been reported in those cases that have recovered from the leukemia.

Eighty-five patients with nodular lymphoma diagnosed between 1968 and 1975 were followed up for long periods and were treated by either conventional methods (local radiotherapy and single drug chemotherapy) or by more intensive therapeutic regimens, such as initial combined M.O.P.P. therapy and maintenance treatment with chlorambucil with or without further courses of M.O.P.P. Long-term follow-ups have brought to light some interesting points concerning the prognosis. Dissemination of the disease and large-cell histological pattern were, as already known, unfavourable factors. Neither age nor sex, nor bone-marrow involvement seemed to have any influence. Obtaining complete remissions improved the prognosis, but intensifying the initial and maintenance treatments proved disappointing: the survival rate remained the same, and the incidence of drug induced leukaemias was high. Indeed, relapses appeared to be less responsive to treatment when the patient had initially received multiple chemotherapy. However, in view of the high death rate of the disease (one-third of the patients in this series died within the first 5 years), trying new therapeutic regimens in the hope of obtaining better results, as has been done in Hodgkin's disease, would be fully justified.

Prognosis in cancer of the upper respiratory-digestive tract (URDT) is dominated by the importance of local and regional spread, of second localizations or metastases and of any underlying clinical condition. Stable results are obtained using local and regional treatment (surgery and/or chemotherapy) alone, and the use of chemotherapy has been evaluated since 1965, neo-adjuvant cancer chemotherapy being adapted in 1970 for cancer of URDT. From november 1982 to december 1983, 184 patients with epidermoid cancer of URDT were treated by combined therapy with Cisplatin, 5 Fluoro-uracil, Bleomycin as a continuous infusion. Results are presented of the different tumoral responses as a function of localization and stage, excluding any glandular responses.

Amongst 1500 cases of acute lymphoblastic leukaemia, affecting both sexes, the authors noted 111 testicular recurrences and 2 ovarian recurrences, i.e. an incidence of 16 percent. Clinical diagnosis is easy and testicular needle biopsy was reserved for doubtful cases only. Amongst 12 lymphographies, only one showed lumbar node involvement. Testicular involvement may exist before, after or in association with a bone marrow or a meningeal relapse. In 47 cases the first signal recurrence was a testicular tumour. The majority of these recurrences occured during the first two years of the disease, but late recurrences affecting the gonads are possible. Mean survival after an isolated testicular recurrence was 14 months, identical with meningeal recurrences. General chemotherapy and local radiotherapy were in general followed by an in situ or contralateral recurrence. Bilateral irradiation at a dose of 2400 rads is the best local treatment. However, in the light of the frequency of bone marrow recurrences a short time after, intensification of general treatment is necessary.

A metastasis from a breast carcinoma developed in the cervical cord. The localisation and nature of the lesion were easily diagnosed by a contrast MRI study with Gadolinium DTPA.

Slides of 198 patients with primary malignant melanoma have been reevaluated independently by three pathologists; considered parameters were histologic type, Clark's level and tumor thickness. The agreement between pathologists is excellent, especially for histologic type and thickness. The use of the Cox's regression model, dealing with disease free interval as response criterion, shows that the main prognostic factor is tumor thickness, whatever the pathologist. A prognostic staging is thus proposed, based only on the tumor thickness, less than 2 mm, greater than 2 mm. The prognostic value of this staging is confirmed on a new sample of 145 patients. This classification is used as decision tool in a new randomized clinical trial.

Neoadjuvant chemotherapy can be used before radiotherapy to combat microscopic metastatic loci and to facilitate irradiation. Improvement in the survival time by impeding the dissemination of metastases seems to be real for breast cancer, but has not been observed to date in randomized studies of ENT cancers. Neoadjuvant chemotherapy in Hodgkin's disease has improved survival time and tolerance to irradiation, allowing a lowering of the total doses used and the volumes irradiated. In breast and ENT cancers, it has become possible, due to tumor regression, to replace mutilating treatments with more conservative ones consisting of radiotherapy alone, without increasing the risk of local relapse. Indeed, it is in this domain that neoadjuvant chemotherapy is the most useful. Two important conditions must be met for its successful application: a) a sufficiently effective regimen must be chosen, in order to prevent tumor growth prior to irradiation (which would aggravate the prognosis); and b) an accurate identification and localization of the tumor before undertaking any treatment so as to not detract from the effectiveness of the radiotherapy.

Seventy-four patients with acute pure monoblastic leukaemia treated between 1970 and 1978 were studied retrospectively. The disease was usually hyperleucocytic and tumoral in character. It occurred with equal frequency in subjects of both sexes and at all ages, with peaks at the two extremes of life. Rubidazone gave a high percentage (75%) of complete remissions, but the prognosis remained sombre, with a mean survival time of 200 days. The incidence of meningeal relapses was reduced by prophylactic measures at central nervous system level, but gingival and cutaneous relapses were frequent. The possibility of bettering the present modest therapeutic results by more intensive chemotherapy is discussed.

In a prospective randomized study, the effect of chemotherapy (either systemic or combined intraarterial and systemic) was studied in 117 patients undergoing a curative resection of Clark's level III, IV or V malignant melanoma. Systemic chemotherapy was started one month after surgery one week courses with an I.V. injection of Vinblastin 6 mg/m2, Thiotepa 6 mg/m2, Rufocromomycine 60 microgram/m2, Methotrexate 15 mg/m2 on day one with procarbazine 30 mg/m2 orally daily were given every other week for three months and later every four weeks. Intraarterial chemotherapy of DTIC 80 mg/kg day for ten days was given 28 days prior to surgery. 65 patients with limb malignant melanoma were treated either by surgery only (27 patients), or by systemic chemotherapy (23 patients) or by preoperative intraarterial chemotherapy and systemic chemotherapy (15 patients): 52 patients with non limb malignant melanoma were treated either by surgery only (28 patients) or by systemic chemotherapy (24 patients). We drew curves of disease free survival following surgery and studied the levelling off of the curves, 24 months after surgery 65% of the patients treated by surgery alone were alive and free of disease whereas 81% of the patients treated by surgery and chemotherapy were alive and free of disease (p less than 0.05) suggesting a possible benefit of adjuvant chemotherapy. Intraarterial preoperative chemotherapy has not proved of additional benefit to date.

Between 1959 and 1973 were analyzed the records of 798 patients with chronic myelocytic leukemia. Mean survival (MS) for the entire group is 42 months. 342 patients have been followed closely during and after development of blastic transformation. Presence of following symptoms at the time of diagnosis: asthenia, weight loss, bone pain, fever, sweats and digestive disorders is of poor prognosis significance (MS: 36 months, no sign: MS 75 months) (P less than 0.001). Spleen size is also a prognostic factor. MS are respectively 70, 52 and 35 months if initial splenomegaly is moderate (less than 3 cm), marked (less than 6 cm) or tumoral (greater than or equal to 6 cm). Thrombocytopenia (less than 15,000/mm3 or thrombocythemia (greater than 1 million/mm3) have a poor prognosis with median survival 22 months and 28 months. If peripheral blast cells (hemocytoblasts + myeloblasts) exceed 5%, the prognosis is worse; beyond 10% MS is 26 months. In contrast certain factors have better prognosis: hemoglobin greater than or equal to 14 g/100 ml, young age (less than 20 y.) MS: 62 months), female sex and an initial WBC count below 25 x 10(3)/mm3 (MS: 70 months).