A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with advanced ovarian, tubal or peritoneal cancer resistant to platinum, taxane and topotecan.

BACKGROUND: DX-8951f is a water-soluble camptothecin derivative with greater in vivo and in vitro activity than topotecan or irinotecan. The objectives of this phase II study were to determine the antitumor activity, safety and pharmacokinetic profile of DX-8951f administered intravenously for five consecutive days, every 3 weeks in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. METHODS: Enrolled in the study at The University of Texas M. D. Anderson Cancer Center were 16 patients with measurable cancer resistant to platinum, taxane and topotecan. All 16 patients were assessable for safety and 15 for efficacy analyses. Treatment consisted of a daily infusion of DX-8951f at 0.3 mg/m(2) per day (except for one minimally pretreated patient who started at 0.5 mg/m(2) per day) over 30 min for five consecutive days every 3 weeks. The pharmacokinetic and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Disease was stable in 7 of 16 patients (44%) (4 minor response and 3 stable disease). The median time to tumor progression was 43 days (95% CI 37-92 days). The median overall survival was 117 days (95% CI 90-279 days). The main toxic effect was neutropenia and leukopenia with 50% of patients experiencing grade 3 or 4 neutropenia and leukopenia. One episode of neutropenic fever was observed. Grade 3 or more anemia and thrombocytopenia were seen in 25% and 13% of patients, respectively. Grade 3 nonhematologic side effects included nausea (25% of patients) and fatigue (19%). Other side effects were not more than grade 2, and included gastrointestinal dysfunction, stomatitis, dermatitis, alopecia, liver dysfunction and drug fever. DX-8951 displayed linear pharmacokinetic characteristics at the doses administered. The average plasma clearance, total volume of distribution, and terminal elimination half-life were 2.1 l/h per m(2), 20 l/m(2) and 9.5 h, respectively. CONCLUSIONS: DX-8951f administered parenterally as a single agent daily at a dose of either 0.5 or 0.3 mg/m(2) per day for 5 days is feasible in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. Although no responses were observed, a significant number of patients had stable disease with a decrease in CA-125 levels. In this heavily pretreated population, DX-8951f has clinically relevant hematologic and gastrointestinal toxicities in about 25% of patients. DX-8951 appeared to have linear pharmacokinetic characteristics on the basis of multiple administrations.

Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks.

Exatecan mesylate (DX-8951f) is a topoisomerase I inhibitor that has increased solubility and antitumor activity compared with other topoisomerase I inhibitors. The purpose of this study was to establish a safe dose of DX-8951f given as a weekly 24-h infusion 3 of every 4 weeks. DX-8951f was administered as a 24-h continuous infusion in escalating doses. Twenty-seven patients were treated with 81 courses of the drug. Dose-limiting toxicities included neutropenia, thrombocytopenia, and inability to administer all three doses in the first cycle. In minimally pretreated patients, a dose of 0.8 mg/m(2) was tolerable. In patients who were heavily pretreated, a slightly lower dose, 0.53 mg/m(2), was tolerated without any severe toxicities. Nonhematological toxicities were mild and consisted of mild diarrhea, asthenia, mild nausea, and constipation. Pharmacokinetic parameters could be well described with a one-compartment model in most patients, although the application of the one-compartment model probably resulted in an underestimated elimination half-life. In conclusion, the recommended Phase II dose for DX-8951f administered as a weekly 24-h infusion on a 3-of-4 week schedule is 0.8 mg/m(2) in minimally pretreated patients and 0.53 mg/m(2) in patients who are heavily pretreated.

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic (PK) profile, and recommended phase II dose of Exatecan mesylate (DX-8951f) when administered as a 24-hour continuous infusion every 3 weeks to patients with solid tumors. PATIENTS AND METHODS: Twenty-two patients with advanced solid tumors, all previously treated, and with performance status < or = 2, were entered. The starting dose of DX-8951f was 0.15 mg/m(2); the dose was escalated according to the modified continual reassessment method. The drug was administered until disease progression or until unacceptable toxic effects occurred. RESULTS: Seven dose escalations were completed, and a total of 53 courses were delivered (median, two courses; range, one to eight courses) during the study. At doses 1.2 mg/m(2) and lower, toxicities were mostly grade 1, primarily hematologic. In the initial cohort of three patients treated at 2.4 mg/m(2), grade 2 hematologic toxicity was observed. Of the six additional patients entered at 2.4 mg/m(2), three had grade 3 or 4 granulocytopenia. At doses higher than 2.4 mg/m(2), DLT granulocytopenia was observed. Nonhematologic toxicities, including nausea, vomiting, diarrhea, fatigue, and alopecia, were mild to moderate. Neither complete nor partial responses were observed, but four patients had stable disease. The PK profile of DX-8951f seemed linear at the doses administered. The plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 3 L/h, 40 L, and 14 hours, respectively. CONCLUSION: The DLT of this DX-8951f schedule was granulocytopenia for minimally pretreated patients, and both granulocytopenia and thrombocytopenia for heavily pretreated patients. The MTD for both minimally and heavily pretreated patients was 2.4 mg/m(2). DX-8951f seems to have a linear PK profile on the basis of single-dose administration. The recommended phase II dose with this schedule is 2.4 mg/m(2) for minimally pretreated patients. A lower dose should be used for heavily pretreated patients.

DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: a phase I and pharmacokinetic study in patients with advanced solid malignancies.

PURPOSE: To assess the feasibility of administering DX-8951f (exatecan mesylate), a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of DX-8951f. After three patients were treated at the first dose level, doses were to be escalated in increments of 100%, using a single patient at each dose level unless moderate toxicity was observed. The MTD, defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%, was calculated separately for minimally pretreated (MP) and heavily pretreated (HP) patients. The PK and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Thirty-six patients were treated with 130 courses of DX-8951f at six dose levels ranging from 0.1 to 0.6 mg/m(2)/d. Brief, noncumulative neutropenia was the most common toxicity observed. Severe myelosuppression (neutropenia that was protracted and/or associated with fever and/or severe thrombocytopenia) was consistently experienced by HP and MP patients at doses exceeding 0.3 and 0.5 mg/m(2)/d, respectively. Nonhematologic toxicities (nausea, vomiting, and diarrhea) were also observed, but these effects were rarely severe. Objective antitumor activity included partial responses in one patient each with platinum-resistant extrapulmonary small-cell and fluoropyrimidine- and irinotecan-resistant colorectal carcinoma, and minor responses in patients with prostate, hepatocellular, thymic, primary peritoneal, and irinotecan-resistant colorectal carcinomas. The PKs of total DX-8951 were linear and well fit by a three-compartment model. CONCLUSION: The recommended doses for phase II studies of DX-8951f as a 30-minute infusion daily for 5 days every 3 weeks are 0.5 and 0.3 mg/m(2)/d for MP and HP patients, respectively. The characteristics of the myelosuppressive effects of DX-8951f, paucity of severe nonhematologic toxicities, and antitumor activity against a wide range of malignancies warrant broad disease-directed evaluations of DX-8951f on this schedule.

DX-8951f: summary of phase I clinical trials.

Exatecan mesylate (DX-8951f) is a new hexacyclic camptothecin analogue with favorable attributes compared to topotecan and CPT-11, including watersolubility, greater potency against topoisomerase I, lack of esterase-dependent activation, broad antitumor activity, and low cross-resistance against MDR-1 overexpressing tumors. In preclinical studies, the compound demonstrated a favorable toxicology profile with hematologic dose-limiting toxicity and moderate gastrointestinal toxicity, linear pharmacokinetics, P450 hepatic metabolism (CYP3A4 and CYP1A2), and predominately fecal excretion. The results of six U.S. and European phase I clinical trials as well as two Japanese studies are presented including total DX-8951 and lactone DX-8951 pharmacokinetics. The toxicity profile was similar for all schedules of administration. Hematologic toxicity was dose-dependent and reversible. Neutropenia was dose-limiting in minimally pretreated patients, whereas neutropenia and thrombocytopenia were dose-limiting in heavily pretreated patients. Non-hematologic toxicity included moderate gastrointestinal toxicity (nausea, vomiting > diarrhea), transient elevation of hepatic transaminases, asthenia, and alopecia. Two cases of acute pancreatitis not predicted by preclinical toxicology were also observed. Antineoplastic activity was detected in several solid tumor types: non-small cell lung cancer, extrapulmonary small cell cancer, colorectal cancer, hepatocellular cancer, and sarcoma. Antitumor activity was seen in CPT-11 and topotecan-resistant tumors. Pharmacokinetics were linear within the dose range tested. A pharmacokinetic/pharmacodynamic model predictive of DX-8951f-induced neutropenia in individual patients was developed. The daily x5, every 3-week schedule with the drug administered as a 30-minute intravenous infusion was selected for future phase II clinical trials based on its superior antitumor activity.

Comparison of DX-8951f and topotecan effects on tumor colony formation from freshly explanted adult and pediatric human tumor cells.

DX-8951f, which shows great therapeutic potential, was tested in the human tumor cloning system in adult and pediatric tumor types against which topotecan has been active. In 47 tumors from adults, DX-8951f had definite cytotoxic activity in a concentration-dependent manner with both 1 h and continuous exposures. Topotecan was minimally effective using a 1 h exposure and showed concentration-dependent inhibition with continuous exposure. In head-to-head comparisons at 1 h exposure against adult tumors, DX-8951f was significantly more effective at 0.1 and 1.0 microg/ml than topotecan. In head-to-head comparisons (continuous exposure), 1.0 microg/ml DX-8951f was more effective than topotecan at 1.0 microg/ml in adult tumors, including three of four head and neck, one of two kidney, two of five liver, six of 10 non-small cell lung, five of eight ovarian, four of eight prostate tumors, and in single specimens of breast, mesothelioma, colon and small cell lung tumors. With continuous exposure, DX-8951f and topotecan were equally effective at equimolar concentrations. The maximum tolerated dose for DX-8951f is 3 times that of topotecan, so higher doses of DX-8951f could be administered to patients. DX-8951f is a promising new antineoplastic agent with significant activity against tumors taken directly from patients.

Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.

Current status of cancer immunodetection with radiolabeled human monoclonal antibodies.

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P < .05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P < .01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.

Long-term complete remission in bladder carcinoma in situ with intravesical TICE bacillus Calmette Guerin. Overview analysis of six phase II clinical trials.

Carcinoma in situ is a form of superficial transitional cell carcinoma, which is characterized by a lateral spread along the bladder epithelium, with high-grade malignancy and poor prognosis. Early radical cystectomy is considered the definitive treatment even in the absence of associated invasive cancer. In six prospective phase II studies, 123 carcinoma in situ patients were administered intravesical TICE bacillus Calmette-Guerin (BCG). Treatment consisted of at least six weekly instillations (induction) followed by twelve monthly instillations (maintenance) of BCG (50 mg: 1 to 8 x 10(8) colony-forming units). Of 119 evaluable patients, 90 (76%) achieved complete remission including 45 of 63 (71%) patients who received prior intravesical chemotherapy. Forty-five responders (50%) remain in complete remission with negative urine cytology with a median duration of response projected to be greater than or equal to forty-eight months. There is no difference in survival between BCG responders and nonresponders, but there is a significant difference in cystectomy rates: 10 of 90 (11%) responders vs. 16 of 29 (55%) nonresponders (P less than 0.0001, Fisher's exact test) and time to cystectomy (31 vs. 74 mos.) (P less than 0.001, log-rank test). Delaying cystectomy does not seem to affect survival and improves quality of life. Treatment was well tolerated with some major adverse effects. Intravesical TICE BCG is an effective treatment for bladder carcinoma in situ patients with or without prior chemotherapy.

Principles of cancer pain management. Use of long-acting oral morphine.

Oral morphine is increasingly recognized as the pharmacologic standard for cancer pain management. Yet for the primary care physician and oncologist alike, misconceptions of the safety and efficacy of oral morphine along with lack of recognized guidelines for use have often resulted in inadequate cancer pain therapy. Use of controlled-release oral morphine sulfate (MSC) requires additional guidelines for optimum analgesia. Proposed are ten principles of dosing oral morphine, especially MSC, which were followed in a clinical trial involving cancer patients. MSC dosed at 8-, 10-, and 12-hour intervals was compared with immediate-release morphine (IRMS) dosed every four hours, and with prestudy analgesics. Patients achieved satisfactory analgesia at daily doses (mean +/- SE) of 118.0 +/- 8.6 mg and 111.4 +/- 12.6 mg (P greater than .05) for IRMS and MSC, respectively. Dosing endpoints were determined by titration with IRMS and MSC to a minimal and equivalent amount of supplemental short-acting analgesic. Side effects were typical for opioids and tolerated except for one dropout on IRMS (nausea and constipation). The ten principles have been incorporated into a dosing scheme as a practical guide for MSC therapy.

Giant basal cell carcinoma with metastases and myelophthisic anemia.

We report a 59-year-old, dark-complexioned black man with a giant basal cell carcinoma infiltrating virtually the entire scalp. Widespread metastatic bone marrow involvement produced a myelophthisic anemia. Basal cell carcinoma is rare in blacks, is rarely this large, and very rarely produces myelophthisic anemia from bone marrow metastases.

Phase II study of elliptinium in advanced breast cancer.

A group of 74 patients with advanced breast cancer received elliptinium as second- or third-line treatment (100 mg/m2/week). The objective response rate was 19% (30% in soft tissue metastases), lasting from 3 to 12 months. This drug appears to have no marrow toxicity. Mild to moderate nausea and mouth dryness were the most frequently encountered side effects. Hemolysis occurred in five patients who had an IgM antibody and represents the dose-limiting toxicity. Cumulative renal toxicity (World Health Organization, grade 2) was observed in one of ten patients who had received greater than 2000 mg of elliptinium.

An EORTC phase II study of mitoxantrone in solid tumors and lymphomas.

Mitoxantrone is an anthracenedione, showing structural similarities to doxorubicin. This drug has been proved active against several tumor systems, including some tumors resistant to doxorubicin, and also against human breast xenografts. It is also less cardiotoxic than doxorubicin. Mitoxantrone has been given to 335 patients in an i.v. perfusion of 12 mg/m2 or 14 mg/m2 every 3 weeks. Two hundred and sixty-three patients with advanced disease were evaluable for response: breast (94 patients), head and neck (40), kidney (20), bronchial (19), lymphomas (13) and various sites (77). Most of the patients had been previously treated with radiotherapy and chemotherapy, including/not including doxorubicin. In breast cancer three complete remissions (CR) and 16 partial remissions (PR) have been achieved (20%). The therapeutic activity was higher in patients who had not received any prior chemotherapy: 35 vs 15% (P = 0.06). The response rate observed at 14 mg/m2 (32%) was superior to the response rate observed at 12 mg/m2 (15%). However, no response has been reported in lung metastases (0/22). The median duration of response is 8 months. Mitoxantrone shows borderline activity in head and neck tumors (one CR and two PR out of 40 patients) but no activity in squamous cells of the lung (0/19). One CR and three PR have been seen out of 13 malignant lymphomas (four Hodgkin's disease and nine non-Hodgkin's lymphomas). The duration of response ranges from 10 to 24+ months. Myelosuppression was moderate and no severe leukopenia has been reported. Nausea and vomiting were seen in 50% of the patients. Four patients presented cardiac events associated with mitoxantrone, such as reversible congestive heart failure or a significant decrease in the ventricular ejection fraction. Alopecia was observed in 17 and 48% of the patients treated with 12 and 14 mg/m2 respectively. Due to its anti-tumoral activity, mainly in breast cancer, and its low hematological and cardiac toxicity, mitoxantrone must be considered as a major antimitotic.

Phase II study of 9-hydroxy-2N-methylellipticinium acetate.

A broad phase II trial of elliptinium was conducted in 105 evaluable patients with advanced solid tumors. The drug was given as a 60-90-min i.v. infusion at a weekly dose of 100 mg/m2. Of 36 breast cancer patients, one achieved complete and six achieved partial response for an overall response rate of 19%. Responses lasted for 12-56 weeks from initiation of therapy. There was also one partial response among 21 patients with squamous cell carcinoma of the lung. No response could be obtained in 17 patients with colon cancer, 13 patients with head and neck cancer and 18 patients with a wide variety of other malignancies. Myelosuppression was minimal. Nausea and vomiting were the most frequent toxic effects. The drug also produced serious xerostomia and acute intravascular hemolysis. Asthenia was common. Other adverse reactions included fever and chills, transient neurologic and cardiovascular manifestations and renal function impairment. Additional work is needed to define optimal modes of drug administration.

Ineffectiveness of inicarone, a fibrinolytic agent, alone or in combination with chemotherapeutic agents on spontaneously metastasizing murine tumours.

The effect of inicarone (L7035), a potent fibrinolytic, alone or in combination, was investigated on spontaneously metastasizing Lewis lung carcinoma (implanted intramuscularly) to verify whether it could prevent the formation of metastases. After intraperitoneal and oral administration, inicarone did not show any cytotoxicity since the survival of animals was not prolonged. Its activity was compared to that of warfarin, an anticoagulant: both drugs were inactive when administered in curative treatment and inicarone even enhanced the number of lung metastases. When administered in combination with cyclophosphamide, an antiproliferative agent, inicarone did not induce any synergism or antagonism, but this combination did not inhibit tumour growth or metastasis spreading. Moreover, when inicarone was combined with a potent antimetastatic agent, Nocodazole, it was shown to be in competition with the latter agent and totally overshadowed its activity; since inicarone had no antimetastatic effect, the number of metastases rose dramatically.

Phase II study of amsacrine in solid tumors: a report of the EORTC Early Clinical Trial-Group.

A total of 239 patients with advanced solid tumors were treated in this phase II trial. Amsacrine was administered as a single i.v. dose of 120 mg/m2 repeated at 21-day intervals. The initial dose was reduced to 90 mg/m2 in the case of extensive prior therapy. Some antitumor activity was detected in head and neck cancer but the drug appears to lack significant efficacy in epidermoid lung cancer as well as in carcinoma of the breast, melanoma, renal cell cancer, colorectal cancer and non-seminomatous testicular cancer. Leukopenia was the major toxic effect encountered in this trial and was similar at 90 and 120 mg/m2.

[Aclacinomycin-A in acute leukaemias and leukaemic non-Hodgkin lymphomas (author's transl)]. / L'aclacinomycine-A dans les leucémies aiguës et les lymphomes non-hodgkiniens leucémiques.

Aclacinomycine-A (ACM), a new anthracycline derivative, was administered intravenously to 50 patients in doses of 10-30 mg/m2/day for periods of 6 to 30 days. Among the 45 patients who could be assessed, 17 were suffering from acute myeloid leukaemia, 19 from acute lymphoid leukaemia and 9 from non-hodgkin lymphoma. The results confirmed those first published by the authors in 1978 and led them to propose new measures aimed at reducing the toxicity of ACM. Depending on the dosage, complete or partial (more than 50%) remissions were obtained in patients with acute myeloid leukaemia. In the 19 patients with acute lymphoid leukaemia, complete remission was observed in 2 and partial remission in 2. Among the 9 patients with non-hodgkin lymphoma, there was 3 complete and 1 partial remissions. ACM did not produce alopecia and, as predicted by the authors' experimental study on hamsters, did not have major cardiac toxicity. The gastrointestinal toxicity, which had forced a reduction of the total dose in the first trial, proved moderate, even with normal dosage.