Contrarily to that which has been observed in some experimental tumors, the clinical data show that it is not possible to take advantage of the semi-synchronisation of tumor cells induced by the administration of cytotoxic drugs or ionizing radiations, either in combination chemotherapy or during the association between radiotherapy (RT) and chemotherapy (CT). The association of RT and CT has obtained excellent results in those human tumors which are both chemosensitive and radiosensitive such as lymphoma, testicular tumors, embryonal tumors, cancers of childhood. However, even in these favorable types of tumors, high doses of RT and CT are required, not significantly lower than those which are delivered when one of the two modalities is used alone. Therefore, the major problem is that of the possible cumulative toxicity of the two modalities. The toxicity appears to be maximum when the two modalities are administered concomitantly; it can be reduced in sequential administration when there is a sufficiently long interval between the various agents. However, sequential associations may cause long delay in the delivery of one of the two modalities and in rapidly growing tumors this delay might be detrimental. This is why an integrated alternating scheme was proposed in which short radiotherapy courses are interdigitated between the courses of chemotherapy, chemotherapy being administered with the conventional scheduling. Preliminary results of this alternating combination are discussed. In small cell carcinoma of the lung and non-Hodgkin lymphoma of poor histologic types, so far the results are promising.

One hundred and thirty three specimens from mammary and ovarian adenocarcinoma and from melanoma were cultured according to an agar/agar clonogenic assay. Melanoma and ovarian cancers exhibited a 70 per cent rate of success for culture; 50 per cent of the mammary adenocarcinomas were successfully cultured. Fifty-nine ovarian cancers were cultured in order to test the in vitro effectiveness of Cisplatinum and Adriamycin. Thirty percent of cultured tumors gave rise to relevant chemograms. The chemoresistance measured in vitro was correlated to the ineffectiveness of the patient's treatment. In contrast, we were unable to predict chemosensitivity. Taking into account the technical difficulties encountered in these assays, human tumor clonogenic assays cannot at present be proposed as a routine procedure in the prediction of the effectiveness of chemotherapeutic treatments. Nevertheless, they must be developed in order to determine the spectrum of activity of new antineoplastic agents on various human tumors.

It now seems possible to predict response to anti-cancer drugs by means of several methods classified into three groups. Methods in the first group are aimed at determining the intracellular mechanisms required for the drugs to act on the tumoral cells; apart from hormone receptor assays, few of these have practical applications. Methods in the second group are concerned with the action of cytostatic drugs on malignant cells; clonogenic cultures and human tumour xenografts in mice are already routinely used. Finally, methods to evaluate the pharmacokinetics of anticancer drugs are being developed. These three groups of methods can be used in the pre-clinical screening of these drugs or at the clinical trial phase to predict individual responses to chemotherapy.

Nephrocalcinosis due to hyperphosphataemia with hypocalcaemia is a rare cause of ARF during chemotherapy of ALL. Three cases are reported, one with renal anatomopathological studies and microanalysis of the intratubular calculi. All possible preventive measures should be taken against this complication which is related to acute tumoral lysis, especially in the hyperleukocytic and/or tumoral forms of ALL.

Infection is the leading cause of illness and death in children with leukemia. The risk of infection may change over time as regimens of therapy are modified. A review of the hospital charts of 166 infants in whom leukemia had been diagnosed between 1976 and 1980 revealed an increased number of deep fungal infections (20 v. 3) during this period in comparison with the number between 1969 and 1976 in 164 patients treated at the same hospital whose leukemia was diagnosed between 1969 and 1975. The 20 severe fungal infections between 1976 and 1980 were characterized by difficulty of diagnosis (a definite diagnosis having been made three times out of four only at autopsy), an important role of Candida but also of Aspergillus (the latter having been isolated almost as often as the former) and a grave prognosis (the mortality being very high [75%] and much above that for gram-positive septicemia [6%] and that for gram-negative septicemia [31%]). This increase in frequency of fungal infections was concurrent with the introduction of phase-1 chemotherapy, which was often responsible for prolonged neutropenia. To reduce the risk of infection in children with leukemia it appears to be essential to improve diagnostic methods and approaches to therapy.

Some aspects of the relationships between malignancy and rheumatic diseases are presented. The incidence of leukaemia and lymphomas is increased in rheumatic patients previously treated by alkylating agents or x-rays; hypertrophic treated by alkylating agents or x-rays; hypertrophic osteoarthropathy is frequently associated with bronchogenic carcinoma; very exceptionally, rheumatoidlike arthritis or polymyalgia rheumatica may be paraneoplastic syndromes. As a rule there is an interval of as long as several months between the beginning of joint or bone pains and radiological appearance of metastases. Early detection is possible if there is an elevated level of alkaline phosphatase, increased excretion of hydroxyproline and a positive bone scan.

Fourteen adult patients with inoperable soft tissue sarcoma (with metastases in 4 cases) received chemotherapy as primary treatment. Nine cases were treated by CYVADIC (cyclophosphamide, vincristin, doxorubicin, DTIC) and five cases by DECAV (DTIC, cyclophosphamide, cis-platinum, doxorubicin, vindesine). An objective response was obtained in 7 cases (1 complete remission and 6 regressions greater than 50%) and stabilization in 4 cases. Seven patients became operable after 2 to 6 courses of chemotherapy and a complete resection could be performed in 6 cases. The duration of the response was 2 to 39 months. Toxicity with both combinations was acceptable. We conclude that chemotherapy can provide initial tumor reduction and permit subsequently less radical surgery.

The results of a combination chemotherapy trial (melphalan, CCNU, vincristine, cyclophosphamide) involving 28 patients with stage III (n = 21) or stage II (n = 7) multiple myeloma suggest a high response rate, with a mean 71% malignant cell destruction in 78.5% of the patients. A longer survival in responsive stage III patients as compared with patients treated with alkylating agents seems likely, but this can only be established by a randomized trial. Despite haematological side-effects, this combination therapy may be used in high risk patients, especially those resistant to a single alkylating agent and in whom the frequency, intensity and duration of responses appears to be the same as in previously untreated patients. In contrast, only one of the 7 patients treated for relapse after previous response to a single alkylating agent responded to the combination chemotherapy.

Chemotherapy is essential for the treatment of malignant diseases in childhood. Monitoring a child on chemotherapy includes: 1) looking for evidences of relapse or metastases; 2) if necessary, adjusting doses according to blood counts; 3) preventing and treating intercurrent infections, which are mostly viral, once the initial regimen is completed; 4) diagnosing and, if possible, treating, harmful side-effects, which cannot always be precluded; 5) helping both patient and family to live a normal life; in this respect, normal school attendance is of particular significance.

Following three courses of induction chemotherapy, 23 patients with small cell carcinoma of the lung were treated with a late intensive regimen including autologous bone marrow infusion. Thirteen patients received high doses (2 or 3 times the induction chemotherapy dosage) of cisplatin, adriamycin and etoposide. One patient was probably cured, but renal and mucosal toxicity was observed. Three patients treated with adriamycin, etoposide and cyclophosphamide also developed severe mucositis. The seven remaining patients received high doses of cyclophosphamide (100 to 200 mg/kg) and etoposide (750 to 1000 mg/m2); responses were obtained with moderate toxicity. The long-term survival is not yet known. The usefulness of bone marrow infusion cannot be determined without further studies.

A new subcutaneous flap technic, derived from the chinese forearm flap has been demonstrated. It has been used to cover large cutaneous defects of the hand, especially when the extensor tendons were exposed. An excellent functional repair has been obtained in a single procedure avoiding large scar formation usually seen on the forearm after classical chinese fasciocutaneous flap.