[The role of neo-adjuvant chemotherapy in breast cancers].
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Biomedical subjects
Publications and source records attributed to D Khayat.
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One hundred and thirty-nine patients were treated between 1980 and 1988 for epithelial cancer of the ovary: 35 stage I, 30 stage II, 66 stage III and 8 stage IV (according to the IFGO classification). For stage I and II patients, who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy followed by combination chemotherapy, the 5 year survival rate without relapse was 91%. For those classified as stage III, the 5 year survival rate was 36%. When the tumor was completely removed surgically, the 5 year survival rate was 82%, but the disease-free (without relapse) rate was only 47%. When the malignancy could not be completely excised, the 5 year survival rate was only 15%. The only chance these patients had to survive was if chemotherapy effectively controlled the residual mass (verified during an exploratory laparotomy). In our experience, the combination of cisplatin, doxorubicin and cyclophosphamide, in spite of a 78% response rate, only histologically eliminated the residual tumor in 15% of the patients.
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We have tested the effects of calcium channel blockade with diltiazem on methotrexate-induced nephrotoxicity in patients with biopsy-proven malignant disease. The patients were randomized in a cross-over fashion to receive MTX (4 g.m-2 body surface area) with or without Diltiazem (360 mg per day orally) during two consecutive periods separated by a 3-week interval. Methotrexate caused reversible acute renal failure, with an increase in serum creatinine from 89 (7)mumol.l-1 on day 0 to 150 (6)mumol.l-1 on Day 6. The patterns of beta 2-microglobulin and N-acetyl glucosaminidase urinary excretion were similar, with a sharp increase from Day 0 to Day 3. Urinary beta 2-microglobulin excretion increased from 161 (57) micrograms.l-1 on Day 0 to 1160 (840) micrograms.l-1 on Day 3 and fell to 918 (530) micrograms.l-1 on Day 10. Urinary N-acetyl glucosaminidase excretion increased from 250 (100) mmol.h-1 per mg of creatinine on Day 0 up to 655 (261) on Day 3 and fell to 285 (82) on Day 10. The evolution of renal function was not influenced by diltiazem. In patients receiving diltiazem, serum creatinine increased from 93 (0) mumol.l-1 on Day 0 to 151 (68) mumol.l-1 on Day 6 (p = NS when compared with control values). Urinary enzyme excretion also markedly increased from Day 0 to Day 3 to the same extent as in the group not receiving diltiazem. Our data indicate that acute deterioration in renal function caused by methotrexate is accompanied by tubular damage. Diltiazem was ineffective in preventing the acute renal failure induced by methotrexate.(ABSTRACT TRUNCATED AT 250 WORDS)
Ninety-eight patients with locally advanced cancer of the breast (stages IIIa-IIIb) observed between March 1981 and March 1986 were included in a study associating initial (neoadjuvant) intensive chemotherapy with or without hormone therapy, in all cases followed by external irradiation and then by maintenance radiotherapy and chemotherapy. A greater than 50% regression in the volume of the tumour was observed in 91% of patients after the initial chemotherapy, a result which was improved by hormone therapy with a complete clinical remission in 100% of cases after external and interstitial irradiation. The incidence of local recurrence was 11%. The 3 and 5 year survival rates without recurrence were 63% and 56% respectively and the global survival rate was 78% and 65% respectively. The degree of tumoral regression after the initial chemotherapy appeared to be the major prognostic factor.
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Thirty-three patients with disseminated malignant melanoma were entered in a phase II study of the new nitrosourea S 10036 using a 100-mg/m2 weekly induction schedule for 3-4 consecutive weeks. Patients who responded to this treatment were followed with a maintenance therapy every 3 weeks. Toxic effects were mainly hematological and consisted of delayed thrombocytopenia and leukopenia. Among 30 patients who could be evaluated, eight partial responses were observed (response rate, 26.67%); among seven patients with cerebral metastasis, two partial responses were observed. This multicentric study is currently being continued to confirm this interim report.
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Cancer immunotherapy still appears very unsatisfactory in humans. However, it has been shown recently that Interleukin 2 (IL2) could be used to generate, in vitro as well as in vivo, a new anti-tumoral activity directed against fresh tumor cells, allogenic as well as autologous, both of leukemic and solid tumor origin. This activity is not connected with the NK activity, but with a lymphocyte sub-population termed 'Lymphokine Activated Killer (LAK) Cells'. The exact nature of these LAK cell precursors is still a matter of controversy: 'nul' lymphocyte, T or NK markers bearing lymphocytes, or different precursors according to the system of activation that has been used. However, after being activation, these LAK cells always express T cell-markers. The activation has a very short lifespan, explaining the need for a prolonged contact of the cells with IL2, and therefore the necessity to continue injecting the lymphokine in vivo. The clinical results that have been reported so far are still very preliminary. The most common treatment protocol consists of 5 days of IL2 injections followed by 5 days of leukapheresis and in vitro activation of the collected cells, and then auto-transfusion of the activated cells and IL2 during the next 5 days. The clinical toxicity encountered is impressive in terms of frequency as well as severity. Clinical activity seems to be relatively weak. Nevertheless, the concept still appears to be very promising.
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.
Diethyl-1-[3-(2-chloroethyl)-3-nitrosoureido]ethylphosphonate (S 10036) is a new nitrosourea that has been evaluated in a clinical trial because of its activity in the National Cancer Institute panel screen and its rational chemical approach. A Phase I study was conducted in 22 evaluable patients with advanced cancers. The drug was given as a slow i.v. infusion over a period of 60 min on days 1, 8, 15, and 22 followed by a 4-week rest period. The dose levels ranged from 25 to 200 mg/m2/week for 4 consecutive weeks using a modified Fibonacci scheme. Thrombocytopenia was the only acute dose-limiting toxicity and started at a dose of 100 mg/m2/week and above. Hematological toxicity was delayed, cumulative, and dose related. Nausea and vomiting were moderate to severe and dose related. Three responses (one complete and two partials) have been noted. Phase II studies of S 10036 are planned at a dose of 100 mg/m2/week for 4 consecutive weeks ("induction therapy") for patients without prior therapy and 100 mg/m2/week for 3 consecutive weeks for those with prior chemotherapy or radiotherapy. Because of the cumulative toxicity, the recommended dose for the second cycle of S 10036 chemotherapy ("maintenance therapy") is 100 mg/m2/week every 3 weeks.
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.
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.
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Acute colectasia may occur in patients under mechanical ventilation. Causative factors include haemodynamic changes, potassium loss, underlying pathology (chronic respiratory failure, cirrhosis) and especially morphine-like compounds used for sedation. Analysis of the results obtained with various treatments suggests that surgery is not justified: caecal perforation is extremely rare in a previous healthy colon; any surgical procedure is hazardous in this type of patient, and colectasia frequently regresses under appropriate medical treatment, even though mechanical ventilation is pursued.
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