GM-CSF Did Not Allow Doxorubicin Dose Escalation in the MAID Regimen: A Phase I Trial. A Southwest Oncology Group Study

Since dose intensity of doxorubicin is correlated with the clinical response of patients with sofl tissue sarcomas and since doxorubicin dose intensity niay be compromised in conibiiiation chemotherapy, we evaluated the use of recoinbinant granulocyte-macrophage colony-stiniulating factor (rGM-CSF) to ameliorate niyelosuppression and allow doxorubicin dose escalation in a phase I trial utilizing the MAID combination [Mesna 2.5 g/m²/day × 4 days, Adrianiyciii (doxorubicin) 15 mg/m²/day × 4 days, ifosfaniide 2.0 g/m²/day × 3 days, dacarbazine 250 mg/m²/day × 4 days; to be repeated every 21 days]. Thirteen patients were treated. The doxorubicin dose for the first 6 patients was at the standard dose of 15 mg/m²/day × 4 days (level I), while the doxorubicin dose for the next 7 patients was escalated by 25% to 18.75 mg/m²/day × 4 days (level 2). tGM-CSF was given at 5 μg/kg/day, days 5-14. All patients experienced moderate to severe tiyelosuppression, with all patients at dose level 2 requiring doxorubicin dose reduction to dose level I or lower by their third course of treatment. rGM-CSF failed to allow sustained escalation of the doxorubicin dose in the MAID reginien.     

Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma

Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done.

Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily × 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m² days 1–3, cisplatin 30 mg/m² days 1–3 and 29–31, and etoposide 50 mg orally days 1–14 and 29–42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m² every 8 weeks × 4 cycles was given after radiation therapy.

Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3–4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m² days 1–3, cisplatin 20 mg/m² days 1–3 and 29–31, and oral etoposide 50 mg days 1–21 and 29–49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m² every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 μg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean ± SD 2 hr and 6 hr plasma concentrations were 0.92 ± 0.43 μg/ml and 0.36 ± 0.12 μg/ml, respectively. Estimated duration of exposure to >0.1 μg/ml etoposide was 10–17 hr.

Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained radiosensitizing concentrations can be achieved with low oral doses of etoposide.     

洛铂联合固定剂量多西紫杉醇二线及以上治疗晚期实体肿瘤的剂量递增研究

背景与目的：恶性肿瘤一线化疗后多出现复发或转移,需要二线及以上治疗。本研究旨在确定洛铂联合固定剂量多西紫杉醇治疗化疗后进展的实体肿瘤时洛铂的最大耐受剂量(maximum-tolerated dose,MTD),并评价其不良反应。方法：应用改良的Fibonacci法进行洛铂剂量递增,固定多西紫杉醇剂量为60 mg/m²,洛铂初始剂量为30 mg/m²,组间递增剂量为5 mg/m²,每21天重复。每组至少3例,如1个剂量组中3例均无剂量限制性毒性(dose-limiting toxicity,DLT)出现,则进入下1个剂量组,直至出现DLT,DLT的低一剂量水平即为MTD。结果：17例患者共完成58个周期化疗,进行3个剂量组的研究(洛铂分别为30、35、40 mg/m²),完全缓解(complete response,CR)0例,部分缓解(partial response,PR)1例,疾病稳定(stable disease,SD)10例,疾病进展(progression disease,PD)3例;有效率(response rate,RR,CR+PR)为7.1%(1/14),疾病控制率(disease control rate,DCR,CR+PR+SD)为78.6%(11/14)。主要不良反应为白细胞下降,3例出现DLT,其中2例发生在洛铂40 mg/m²组。确定洛铂35 mg/m²组为MTD。结论：本组洛铂联合固定剂量多西紫杉醇的MTD为35 mg/m²,其不良反应可耐受。     

Combination Cisplatin and Carboplatin in Advanced Squamous Cell Carcinoma of the Head and Neck

Twenty-three patients with advanced squamous cell carcinoma of the head and neck who had received no prior chemotherapy were treated with carboplatin 350 mg/m² followed by cisplatin 50 mg/m² every 28 days. Twenty-one of 23 patients were evaluablefor response and toxicity. Eight patients (38%) achieved complete response (CR) or partial response (PR) with 2 CR and 6 PR. The overall median survival was 8.4 months (range 19 days-56% months). The major toxicity was hematological with grade III/IV granulocytopenia in 32% and grade III/IV thrombocytopenia in 32%. There was very little nonhematological toxicity and no nephrotoxicity. There were no therapy-related deaths. The combination carboplatin/cisplatin is tolerable in patients with squamous cell carcinoma of the head and neck, with objective responses in 38%; however, the response rate was not superior to single-agent carboplatin or cisplatin. Further studies with a higher dose of cisplatin should be considered.     

Phase I and pharmacodynamic study of Triapine,a novel ribonucleotide reductase inhibitor,in patients with advanced leukemia

In a phase I study, 24 patients with refractory leukemia received Triapine^®, a novel ribonucleotide reductase (RR) inhibitor, as a continuous intravenous infusion over 96 h beginning on days 1 and 15 or days 1 and 8. On the days 1 and 15 regimen, the starting dose was 120 mg/m² per day, and the maximum tolerated dose (MTD) was 160 mg/m² per day. Three of eight patients receiving 160 mg/m² per day in the first course, and one patient escalated to this dose in a second course, developed hepatic dose-limiting toxicity (DLT). For the days 1 and 8 regimen, the first 96 h infusion was administered at a fixed dose of 140 mg/m² per day. The dose of the second infusion beginning on day 8 was escalated from 120 to 160 mg/m² per day without observing DLT. No objective responses occurred. Over 70% of patients had a >50% reduction in white blood cell counts. The steady-state levels of Triapine were between 0.6 and 1 μM. As expected from the in vitro studies, at these plasma concentrations there was a decline in dATP and dGTP pools and a decrease in DNA synthetic capacity of the circulating leukemia cells. Based on these clinical, pharmacokinetic, and pharmacodynamic data, Triapine warrants further study in patients with hematologic malignancies.     

Evaluation of Two Consecutive Regimens in Advanced Gastric Cancer

Treatment of gastric cancer still presents a challenge in cancer chemotherapy. In our Institute, from January 1981 to November 1984, 45 patients were given 5-fluorouracil (5FU) 600 mg/m² Days 1, 8, 29, and 36; doxorubicin (A) 30 mg/m² Days 1 and 29; mitomycin-C 10 mg/m² Day 1 (FAM regimen) every 8 weeks. From December 1984 to October 1986, 26 patients were treated with 5FU 300 mg/m² on Days 1-5, A 40 mg/m² on Day 1, cisplatin (P) 100 mg/m² on Day 1 (FAP regimen) every 3 weeks. In the FAM group, 42 patients are evaluable for response; 5 (12%) partial remission (PR), 9 stable disease (SD), and 28 progressions (PRO) were observed. Median duration of response (MDR) was 21 weeks (range 13-45) and the median survival (MS) in the whole group was 27 weeks. In the FAP group, 23 patients are evaluable: 2 CR (9%), 11 PR (47%), 2 SD (9%), and 8 PRO (34%) were observed; CR duration was 24 and 107+ weeks, respectively, MDR of PR was 22 weeks (5-35). The MS of all patients was 16 weeks. Toxicity (WHO criteria) was mild in the FAM group and severe in the FAP group. In spite of a higher objective response rate, the short MS and the severe toxicity observed in the FAP group do not merit recommendation of this regimen in patients with gastric cancer; therefore neither FAM nor FAP appear to be an ideal standard therapy.     

Platinum-Based Chemotherapy Followed by Radiation Therapy of Locally Advanced Nasopharyngeal Cancer a Retrospective Analysis of 39 Cases

A retrospective analysis was performed of 39 patients with locally advanced nasopharyngeal cancer treated with combined chemotherapy and radiation therapy during the last five years, at our departments. There were 26 men and 13 women with median age 55 (24-75) years. Histology was squamous cell carcinoma in 6 patients and undifferentiated carcinoma in the remaining 33 patients. Induction chemotherapy consisted of either regimen A (cisplatin 100mg/m² day 1, 5-FU 1000mg/m² days 2-6 as continuous infusion, bleomycin 15 mg days 15 and 29 i.m., mitomycin 4mg/m² day 22 and hydroxyurea 1 000mg/m² daily days 23-27) or regimen B (carboplatin 300mg/m² day 1, 5-FU 1 000mg/m²days 1-5 as continous infusion and methotrexate 1.2g/m² day 14 with leucovorin rescue). After completion of induction chemotherapy 13 patients (33%) had complete remission (CR) and 19 (49%) partial remission (PR). The CR rate was increased after radiation therapy to 72%. Survival rates were 88% at 12 and 78% at 24 months. Median time to progression was 29.5 months. In conclusion, induction chemotherapy with a platinum-based regimen followed by radiation therapy achieved a high rate of local control. If the treatment also prolongs survival must, however, be studied by randomized trials.     

Cisplatin and Ifosfamide in Patients with Advanced Squamous Cell Carcinoma of the Uterine Cervix A phase II trial

Thirty patients with advanced squamous cell carcinoma of the cervix were included in a phase II study with cisplatin (DDP) and ifosfamide (IF)/mesna. They received a median of 4 courses of chemotherapy and were all evaluable for response and toxicity. Each cycle consisted of 2 500 mg/m² IF i.v. days 1-5; mesna 500 mg/m² i.v. at hours 0 and 2, and 1 000 mg/m² per os at hours 6 and 10, days 1-5; DDP 20 mg/m² i.v., days 1-5. Cycles were repeated every 4 weeks. One patient obtained CR and 14 PR giving an overall response rate of 50%. Mean duration of response was 21 months. Anemia grade 3 developed in 7 patients, leukopenia grade 3 in 9 patients and grade 4 in one patient; thrombopenia grade 3 in 2; creatinine clearance grade 3 in one; CNS grade 3 in one and cystitis grade 3 in one patient. Overall median survival time was about 25 + months (3-63 +); after a follow-up of 70 months, 11 patients (37%) are still alive with a median survival of 31 + months. IF plus DDP seems to be a good combination for treatment of advanced cervical cancer, with acceptable tolerance and response rate.     

A Phase I Trial of Combination Chemotherapy Employing Carboplatin, Vinca Alkaloids, with or without Bleomycin in Patients with Advanced Malignant Tumors

A Phase I trial of three carboplatin-based combination chemotherapy regimens was conducted. These included: carboplatin plus vindesine; carboplatin, vindesine, plus bleomycin; and, carboplatin plus vinblastine. Carboplatin was administered every 28 days as an intravenous bolus. The initial dose was 150 mg/m² and doses were escalated by 50 mg/m² in each successive group of patients. Vindesine was given at a dose of 3 mg/m² weekly for 5 doses, then every other week thereafter. Bleomycin, 10 units/m² IV bolus, was followed by 10 units/m²/day infusion for 4 days (3-7 and 31-35). Vinblastine was given at 5 mg/m² every other week. Doses of vindesine, vinblastine, and bleomycin were not escalated. The maximum tolerated dose (MTD) of the carboplatin, vindesine bleomycin regimens was reached at a carboplatin dose of 250 mg/m² and the MTD was influenced by the weekly vindesine in the initial 4 weeks of therapy. The MTD of the carboplatin and vinblastine regimen was reached at a carboplatin dose of 500 mg/m². Dose-limiting toxicity of all three regimens was leukopenia. Although nonhematological toxicity of the carboplatin and vinblastine regimen included peripheral neuropathy and emesis, therapy was easily administered in an outpatient setting. The recommended Phase II dose of carboplatin is 450 mg/m² in combination with vinblasrine at this dose and schedule for previously untreated patients. Twelve patients demonstrated major responses with the various regimens including 5 of 24 patients with adenocarcinoma of the upper gastrointestinal tract.     

Phase II trial of Paclitaxel and Dacarbazine with filgrastim administration in advanced malignant melanoma

A Phase II trial was conducted in patients with advanced malignant melanoma with intravenous Paclitaxel and Dacarbazine (DTIC). The initial starting dose for Paclitaxel was 135 mg/m² followed by DTIC 800 mg/m². Due to the lack of myelosuppression and other toxicities, the starting dose for Paclitaxel was escalated to 250 mg/m² and the dose for DTIC escalated to l000 mg/m². Twenty-five patients were enrolled in this study. Among the 25 patients assessable for response, three patients had a partial response with a response rate of 12% (CI 3-31%) and one patient had stable disease. Three additional patients showed evidence of anti-tumor activity with minor responses. For patients who had no prior chemotherapy or biochemotherapy, the response rate was 20%. Toxicity was generally tolerable and included mainly neurotoxicity from Paclitaxel. At the doses and schedule used, the combination of Paclitaxel and DTIC did not appear to increase the response rate compared to each agent used singly.     

Phase I-II study of gemcitabine and paclitaxel in pretreated patients with stage IIIB-IV non-small cell lung cancer

Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I–II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m² on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m² on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m²; the paclitaxel dose level just below (210 mg/m²) was selected for phase II evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23–57%). Median duration of response was 35 weeks (range, 8–102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8–108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.     

Phase I-II Trial of High-Dose Melphalan in Previously Untreated Stage III Multiple Myeloma: Cancer and Leukemia Group B Study 8512

To study the efficiency of high-dose melphalan in previously untreated patients with advanced myeloma, we performed a Phase I-U trial. Twenty-eight patients were treated at dose level of 60-140 mg/m². Each patient was first treated with a priming dose of cyclophosphamide (300 mg) followed by high-dose melphalen 1 week later. One course of therapy was given. Patients were then followed without further therapy until relapse. Clinical and laboratory features of the 28 patients in this study included: median age 63, performance status 0-2, hypercalcemia 21%, bone pain 82%, paraprotein types: IgG 76%, Iga 20%, and paraproteinuria 71%. Because none of the patients acheived complete remission (CR) at 60 mg/m², despite life-threatening toxicity in all patients, the dose level was rapidly increased to 140 mg/m², a dose previously reported to induce a high percentage of CR. At this dose, CR was achieved in only 1 of 11 patients (9%). This patient had multiple plasmacytomas without generalized bone marrow involvement. One additional patient at 100 mg/m² achieved CR Of the whole group, 12 achieved PR. Durations of remissions were generally short: CR 6.3 and 18+ months and PR 2.3-18 month, median 6.9 months. Life-threatening myelosuppression was universal with prolonged pancytopenia. Treatment-related deaths from sepsis were observed in 29% of patients. The median survival of the entire group was 15.6 months. Older patients in this trial did not tolerate high-dose melphalen therapy well; this resulted in a high proportion of toxic deaths and poor overall survival.     

Bendamustine/Mitoxantrone/Rituximab (BMR): a very effective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positive indolent malignancies. Final results of a pilot study

We have developed a new chemoimmunotherapy for patients with relapsed or refractory CD20-positive indolent lymphomas and CLL by combining the chemotherapeutic agents Bendamustine (B) and Mitoxantrone (M) with the monoclonal antibody Rituximab. Treatment consisted of (B): 90 mg/m² (80 mg/m² in CLL) day 1 + 2, (M): 10 mg/m² day 1 and (R): 375 mg/m² day 8,15,22 and 29. BM was repeated 3 times starting on day 36, thereafter every 4 weeks. The maximal therapy consisted of 1 × BMR followed by 5 × BM. We have treated 54 patients with BMR. Median age was 68 years (36 - 82). Disease distribution was as follows: 21 B-CLL, 1 B-PLL, 8 lymphoplasmacytic, 14 follicular, 2 mantle cell, 2 marginal zone, 6 secondary high grade. Median number of previous treatments was 2 (1 - 7). ORR was 96% with 41% CR and 55% PR. Median time to progression is 17 months in CLL and has not been reached in indolent lymphomas with a median observation time of 27 months (3 - 60 + ). The time to next antilymphoma treatment is prolonged significantly by BMR. No therapy associated death or hospitalization occurred within the study period. BMR is a well tolerated very effective outpatient treatment for relapsed and refractory CD20-positive indolent lymphomas and CLL.     

A Phase I Study of Escalating Interferon Alpha-2A Combined with 5-Fluorouracil and Leucovorin in Patients with Gastrointestinal Malignancies

On the basis of preclinical data showing synergy between 5-fluorouracil (5-FU), leucovorin (LV) and IFN-alpha-2a, a phase I study was carried out to determine the maximum tolerable dose (MTD) of IFN-alpha-2a with this combination in patients with gastrointestinal malignancies. The treatment consisted of 370 mg/m² 5-FU and 200 mg/m², LV on days 1 to 5, and IFN-alpha-2a on days 1 to 5 of the first week of chemotherapy and on days 1, 3, 5 of each subsequent week, on a 28-day cycle. Six patients with colorectal, 3 with pancreas, 2 with oesophagus, 2 with hepatocellular and one with gastric cancer were treated. At level III (5 × lo⁶ U/m²) all patients experienced grade 3 or 4 toxicity during the first 56 days of treatment and the MTD was declared level II. Grade 3 toxicity comprised of anorexia, mucositis, diarrhoea, and fatigue; in one instance, grade 4 neutropenia occurred. Ten patients were evaluable for response, one patient with an oesophageal cancer had a minor response and one patient with rectal cancer and liver metastases had a radiological complete response lasting 3 months. The recommended dose for this schedule in phase TI studies is 5-FU 370 mg/m², LV 200 mg/m², and IFN-alpha-2a 4 × 10⁶ U/m².     

培美曲塞与多西他赛联合铂类一线治疗晚期肺腺癌的疗效比较

背景与目的：目前,晚期肺腺癌主要依靠以化疗为主的综合治疗。培美曲塞作为一种多靶点抗叶酸制剂,与铂类药物联合应用治疗晚期肺腺癌,因其疗效好、不良反应轻而受到推崇。本研究比较培美曲塞与多西他赛联合铂类一线治疗晚期肺腺癌的效果及不良反应。方法：将50例晚期肺腺癌患者随机分为培美曲塞＋顺铂(PC)组和多西他赛＋顺铂(TP)组。每组各25例患者。PC组：培美曲塞500 mg/m²静脉滴注,第1天;顺铂75 mg/m²静脉滴注,第1天。TP组：多西他赛75 mg/m²静脉滴注,第1天;顺铂75 mg/m²静脉滴注,第1天。两组1个周期均为21 d。比较两组的有效率(response rate,RR)、疾病控制率(disease control rate,DCR)、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。测定外周血T淋巴细胞亚群活性,评价两组患者免疫功能。结果：50例患者均可评价疗效及不良反应,两组均无完全缓解(complete remission,CR)病例,部分缓解(partial remission,PR)20例,疾病稳定(stable disease,SD)17例,疾病进展(progressive disease,PD)13例。PC组与TP组的RR、DCR、PFS和OS差异均无统计学意义(P>0.05)。PC组治疗后与TP组相比,CD3^＋、CD4^＋、CD4^＋/CD8^＋T细胞和NK细胞活性均升高,CD8^＋T细胞活性降低,但差异无统计学意义(P＞0.05)。两组的不良反应主要为骨髓抑制和消化道反应,PC组Ⅲ~Ⅳ级不良反应白细胞减少、血小板减少、消化道症状和乏力的发生率低于TP组,差异有统计学意义(P<0.05)。结论：培美曲塞与多西他赛联合顺铂治疗晚期肺腺癌的临床疗效相当,但前者可降低不良反应发生率。     

Phase II-Trial of Double-Consolidation Following Intensive Induction Treatment for Improvement of Survival in Elderly Patients with Acute Myeloid Leukemia

Thirty-two consecutive, unselected acute myeloid leukemia (AML) patients (pts) of all FAB-subtypes with a median age of 68 years were treated with intensive induction chemotherapy consisting of one or two cycles of daunorubicin 30 mg/m² day 1-3 and Ara C 100 mg/m² as continuous infusion day 1-7. The overall CR rate was 50%, 14/24 (58%) in de novo AML, and 2/8 (25%) with preceding MDS. One patient achieved a PR of 21 months duration, 3 pts died within 7 days of the induction treatment (ED), 6 died during hypoplasia (HD), and 6 remained refractory to 2 cycles of induction. Four pts died after achieving CR. Of the remaining 12 responders, 11 pts received 2 cycles of consolidation consisting of daunorubicin 30 mg/m² day 1, and Ara C 100 mg/m² continuous IV infusion day 1-7. No deaths were observed during consolidation. DFS and survival of responders were 7 and 13 months respectively, survival of all pts, responders and non-responders, was 7 months. Large cooperative trials are necessary to identify those elderly pts who may benefit from intensified consolidation treatment.     

Concomitant Radiotherapy and Daily Low-Dose Carboplatin in Locally Advanced, Unresectable Head and Neck Cancer Definitive results of a phase I-II study

The combination of daily low-dose carboplatin and radiotherapy was studied in 55 patients with inoperable head and neck cancer. All patients were planned to receive 70 Gy plus carboplatin i.v. daily, 45-60 min before radiotherapy. A starting schedule of 30 mg/m² on days 1 through 5, weeks 1, 3, 5 and 7 was administered to 17 patients; an escalating daily dose, up to 55 mg/m² was given to 38 additional patients. Up to a daily dose of 45 mg/m² only 4.4% of the patients developed grade 3 leukopenia; on the contrary, grade 3 and 4 leukopenia was seen in 62.5% of patients receiving 50 mg/m² or more. Mucositis was the major nonhaematologic toxicity and seemed to be dose-dependent. At the end of the loco-regional treatment there were 33 (61.1%) CR and 17 PR; the most effective total carboplatin dose seemed to be 40-45 mg/m². After surgical salvage the number of CRs increased to 37 (68.5%). One-and 2-year loco-regional control rates were 64% and 53% respectively. One- and 2-year actuarial survival rates were 71% and 53% respectively; the corresponding rates of disease-free survival were 60% and 43%. There was a strong correlation nodal status and both survival and disease-free survival.     

Idarubicin plus Cytarabine versus Doxorubicin plus Cytarabine in Induction Therapy for Acute Non- Lymphoid Leukaemia: A Randomized Trial

A randomized trial comparing idarubicin plus cytarabine (IDA/Ara-C) with doxorubicin plus cytarabine (ADM/Ara-C) in induction therapy for ANL,L was carried out. The IDA/Ara-C regimen consisted of idarubicin 20 mg/m² p.o. given on days 1, 2 and 3 plus cytarabine 25 mg/m² as a loading dose followed by 100 mg/m² by continuous infusion daily × 7 days. The ADM/Ara-C regimen consisted of adriamycin 30 mg/m² on days 1, 2 and 3 and the same dose of cytarabine.

Patients who responded to the first cycle with at least 502, reduction of marrow blasts received a second treatment cycle followed by a consolidation cycle of the same treatment for those in CR at the end of 2 cycles. 35/52 (6770 receiving ADM/Ara-C achieved CR, with 25 (48%) patients in CR after a single treatment cycle. 28/48 (58%) receiving ADM/Ara-C achieved CR of whom 11 (23%) went into remission after the first treatment cycle. IDA/Ara-C caused less nausea and vomiting, less stomatitis, a shorter duration of neutropenia and less need for platelet support than ADM/Ara-C. The median duration of CR is 62 weeks for IDA/Ara-C and 48 weeks for ADM/Ara.-C. These differences are not statistically significant. Clinical cardiotoxicity occurred in 4/48 patients treated with ADM/Ara-C. No clinical cardiac toxicity was observed in those receiving IDA/Ara-C. The mean post-treatment ejection fraction was, in addition, lower for ADM/Ara-C than for IDA/Ara-C. It is concluded that IDA/Ara-C is an effective and safe induction therapy for ANLL.     

A Phase I dose-finding study using an innovative sequential biweekly schedule of irinotecan followed 24 hours later by capecitabine

Background: Irinotecan and capecitabine have a broad spectrum of activity in human malignancy and are synergistic in an animal model when irinotecan precedes capecitabine. Patients and Methods: A Phase I design of the combination of irinotecan IV Day 1 with capecitabine on Days 2-8 every 2 weeks was evaluated in 27 adult patients with solid tumors. Two sequential schema were used: Arm A fixed the dose of irinotecan at 100 mg/m² and escalated capecitabine in cohorts, and arm B fixed the dose of capecitabine at 750 mg/m² PO BID and escalated the dosage of irinotecan. Results: Neutropenia was dose limiting with nausea and diarrhea as the most common nonhematological toxicities. Significant interpatient variation in toxicity occurred despite uniform dosing. No Grade IV toxicities were encountered. Grade III toxicity occurred in first cycle in 15 percent (3/20) patients in arm A and 29 percent (2/7) of patients in arm B. All toxicities were reversible. Repetitive dosing was feasible with prolonged disease stabilization in 8 patients. Conclusions: The suggested Phase II dose of this combination and schedule is irinotecan 100 mg/m² and capecitabine 1000 mg/m² BID. Some patients tolerated a capecitabine dose as high as 1250 mg/m² BID.     

持续低剂量去甲长春碱合并顺铂治疗晚期非小细胞肺癌的疗效研究

目的：比较NP方案（去甲长春碱,顺铂）与低剂量去甲长春碱（NVB）持续静脉注射加顺铂（DDP）治疗晚期非小细胞肺癌的疗效及毒副反应,方法：65例晚期非小细胞肺癌患者,持续组31例,应用低剂量NVB持续静脉注射加DDP方案,DDP 20mg静脉注射第1－7天,NVB 10mg静脉注射24小时第1－7天,21天为一周期,两周期评价疗效及毒副反应,对照组34例应用NP方案,NVB 25mg/m^2静脉注射第1,8天,DDP 30mg/m^2静脉注射第1－3天,结果：治疗组CR1例,PR12例,SD15例,PD3例,治疗有效率41．9％,对照组CR1例,PR14例,SD15例,PD4例,治疗有效率44．1％,两组无显著性差异（P＞0．05）,毒副反应：持续组胃肠道反应,静脉炎发生,白细胞减少程度显著低于对照组,结论：低剂量持续NVB静脉注射顺铂治疗非小细胞肺癌与NP方案疗效相似,毒副反应明显减少。