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Direct comparison of peripheral T-cell lymphomas with their B-cell counterpart.

The aim of this study was to determine the effect of immunophenotype on the clinical characteristics and prognosis of 144 adult Chinese patients with non-Hodgkin's lymphomas. Those entities with well-recognised immunophenotype and clinical characteristics were excluded. Significantly more patients with T-cell lymphomas had B symptoms (52 vs. 30%, p = 0.05) and fewer had bulky disease (7 vs. 25%, p = 0.04). Extranodal involvements of liver, spleen, marrow, nasal region and skin were significantly more common in T-cell lymphomas. On the other hand, gastro-intestinal involvement was more commonly seen in B-cell tumours. Induction chemotherapy of comparable intensity was used in treating these patients. The immunophenotype did not appear to affect significantly their prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

1-(2-Chloroethyl)-cyclohexyl-nitrosourea-induced remission in essential thrombocythemia.

14 patients with essential thrombocythemia (ET) and 1 patient with agnogenic myeloid metaplasia received (1-(2-chloroethyl)-cyclohexyl-nitrosourea (CCNU), 80 mg/m2, p.o., in a single dose once a month up to three times. Remission was achieved in 13 patients (86.6%) and easily maintained by low-dose busulfan (2 mg twice a week). The data on the treatment of ET reported in the literature have been reviewed and compared to our results.

Adult↗

[Clinical and therapeutic study (phase II) using VP-16/213 and methyl-CCNU in patients with inoperable, recurring or metastasizing carcinomas of the gastriointestinal tract].

We carried out a phase-II-study in patients with tumors of the gastrointestinal tract, in order to test the effectiveness of the combination of VP-16/213 and ME-CCNU. We studied 15 patients (3 carcinomas of the stomach, 12 colon carcinomas) in a mostly advanced state of illness (disseminated, n = 13). One patient with gastric cancer attained a partial remission with a duration of remission of 9.1 months and a survival time of 14.1 months; the other two patients with cancer of the stomach were non-responders. 1 of 12 patients with colon carcinoma showed a partial remission (PR) (= 8.3%, or 12.5% in untreated patients n = 8), 7 patients showed no change (NC = 58.3%) and 4 patients had progressive disease (PD). The median duration of remission was 4.9 months, the median survival time 7.9 months. With reference to the success of therapy the median survival time was 10.5 months for patients with partial remission and no remission compared with 4.7 months for patients with progression. Toxicity consisted of nausea and vomiting (n = 11), loss of appetite (n = 10), granulocytopenia (n = 9), thrombocytopenia (n = 8) and hairloss (n = 8). The results achieved are comparable to those of monotherapy with the nitrosoureas.

Adult↗

[Ifosfamide versus ifosfamide + CCNU in the treatment of inoperable small cell carcinoma of the lung. A clinical study].

55 selected patients with inoperable small cell carcinoma of the lung have been induced in a randomized prospective trial in order to compare the efficacy of ifosfamide monotherapy with the combination of ifosfamid + CCNU. Initially a control group, treated with symptomatic therapy only, was also included but preliminary analysis revealing that results were unfavourable in comparison to those of the chemotherapy group; this treatment arm was omitted. 53 of 55 patients were evaluable. In group 1 (symptomatic therapy) results were better as to patients' quality of life, but no tumor remissions have been observed and survival times were significantly shorter (15 to 122 days; geometric mean 42.35 days). In group 2 (ifosfamide monotherapy) one total remission (lasting 15 months) and 2 partial remissions (lasting from 3 weeks to 4 months) have been achieved; in this group survival was 3 to 473 days (geometric mean 110.15 days). In group 3 (ifosfamide + CCNU) 7 partial remissions have been observed (3 weeks to 4 months), survival was 17 to 477 days (geometric mean 107.32 days). The combination of ifosfamide with CCNU did not reveal any advantage in comparison to ifosfamide monotherapy.

Adult↗

[Etretinate (Ro 10-9359, Tigason) and CCNU (1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea) and bleomycin versus CCNU and bleomycin in the treatment of advanced squamous cell carcinoma of the bronchus (Working group on Internal Medicine Oncology Study BS1/78)].

Forty-six evaluable patients with advanced squamous cell carcinoma of the lung were treated in a randomized fashion with either etretinate, CCNU and bleomycin in combination (ECB) or with CCNU and bleomycin (CB). There were no complete and no partial responses. Minor responses occurred in 5 patients (24%) with ECB and in 3 patients (12%) with CB independently of histological grade. No change was observed in 9 patients (43%) with ECB and in 13 patients (52%) with CB. There was no survival difference between the two groups. Reversible side-effects of skin and mucous membranes were more frequent under ECB. The antitumor efficacy of CB is marginal and could not be improved by the addition of the vitamin-A-derivative etretinate.

Adult↗

[3 multicenter phase II studies of the treatment of small cell bronchogenic carcinoma (incl. AIO studies BI + BII)].

Between March 1979 und January 1983 122 patients with small-cell carcinoma of the lung were treated with different polychemotherapy regimen. 33 patients received VP-16-213 (etoposid), ifosfamide and vindesine (VPIV). 37 patients were treated with adriamycin, cisplatin and vincristine (APO). A third 3-drug combination, cyclophosphamide, methotrexate and CCNU (CMCC), was given to the remaining 52 patients alternating with the two other regimen. Response rates varied between 61% for the APO regimen and 85% for the VPIV regimen. The median survival was 10 months for patients treated with VPIV or APO and 12 months for patients treated with alternating drug combinations. This difference was not statistically significant. The rate of long-term survivors (longer than 2 years after diagnosis) was 9.9%. Side effects were seen more frequently in the group treated with APO.

Adolescent↗

[Intermediate results of the German Hodgkin's disease therapy study].

Between July 1982 and June 1985 235 out of 436 untreated patients with Morbus Hodgkin's disease qualified for the protocols HD1 (stage IA to IIIA with risk factors), HD2 (stage IIIA) and HD3 (stages IIIB and IVA/B). Patients in HD1 received a combined radiochemotherapy (4 courses + 40 Gy EF vs. 4 courses chemotherapy + 20 Gy EF). In HD2 patients were randomized into TNI 40 Gy vs. 6 courses chemotherapy + 20 Gy IF. Patients in HD3 in complete remission (CR) after 6 courses chemotherapy were randomized into a consolidation therapy 20 Gy IF vs. 2 courses chemotherapy. Chemotherapy of the first 64 patients was COPP, 78 patients received COPP/ABVD. The complete remission rates in HD1 were 76% (COPP) resp. 73% (COPP/ABVD), in HD3 31% (COPP) resp. 62% (COPP/ABVD). Whereas COPP and COPP/ABVD achieved similar remission rates in low stages (HD1), the combination COPP/ABVD seems to be superior to COPP alone for stages IIB/IVA/B (HD3).

Antineoplastic Combined Chemotherapy Protocols↗

[Therapy studies of the German Hodgkin's Study Group. Intermediate results of the study protocols HD1, HD2, and HD3].

Between July 1983 and September 1986 358 untreated patients with Hodgkin's lymphoma qualified for the protocols HD1 (stages I to IIIA with risk factors), HD2 (stage IIIA), and HD3 (stages IIIB and IVAB). Patients in HD1 received a combined chemo-radiotherapy (2 X COPP/ABVD + 40 Gy EF vs. 2 X COPP/ABVD + 20 Gy EF). Patients in HD2 were randomized into radiotherapy (TNI 40 Gy) vs. combined chemo-radiotherapy (2 X COPP/ABVD + 20 Gy IF). Patients in HD3 received induction chemotherapy (3 X COPP/ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 X COPP/ABVD). In HD1, 51 out of 65 evaluable patients (78%) achieved a complete remission. The survival of HD1 patients is as good as the survival of patients in stages I and II without risk factors. In HD3, 58 out of 93 patients (62%) achieved complete remission after induction chemotherapy with COPP/ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 71% complete remissions in stages IIIB/IVAB were achieved. The progression-free survival of HD3 patients who received consolidation therapy is significantly longer than of patients who refused consolidation therapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Oral polychemotherapy in far advanced recurrences of Hodgkin's disease].

In 10 patients with heavily pretreated Hodgkin's disease (stage IVA or IVB) a third-line salvage therapy consisting of CCNU, etoposide and chlorambucil (CECh) was tested. All patients were resistant to both COPP and ABVD. Acceptance and tolerance of CECh were very satisfactory. The observed response rate (3 complete remissions and 4 partial remissions) is encouraging. The survival time after CECh therapy is in excess of 32 months (complete remission) and 15 months (partial remission). The main possible adverse effect is a prolonged myelosuppression. The CECh therapy is an effective alternative chemotherapy in patients resistant to both COPP and ABVD, moderately toxic, easy to administer and well tolerated in heavily pretreated patients.

Administration, Oral↗

Alternating chemotherapy in small cell lung cancer.

Based on the hypothesis of Goldie and Coldman, rapid cyclic alternating chemotherapy has been supposed to be a favorable treatment modality in small cell lung cancer. This approach has been tested in a large series of trials since the late 70's. A few trials performed randomization between alternating and continuous treatment after a period of initial common continuous therapy. The results of these studies are controversial and their interpretation is complicated by the effects of the continuous pretreatment. Recently, most trials were designed as 2-arm approaches with a comparison of continuous standard therapy based on the CAV- or CMC-protocol with an alternating schedule often consisting of the CAV- or CMC-derived combinations and a second regimen including cisplatinum and/or etoposide. In these trials the addition of the second regimen in the alternating treatment arms has improved the treatment results. However, these trials could not clarify whether this advantage was due to the concept of alternating treatment or to the high activity of new drugs given early in the course of therapy in the alternating treatment arms. To ameliorate this weakness, 3 studies were designed as 3-arms approaches using both alternating protocols as continuous control arms. Whereas one investigation noticed an advantage of the alternating schedule, the two others observed no difference. These studies did not report their criteria for shifting non-responding patients from continuous treatment to second line therapy. The longer these patients stayed on the continuous protocol the more the study design favoured the alternating therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Combination chemotherapy in disseminated melanoma and other solid tumors in adults.

Eighty-eight patients with disseminated melanoma and 22 patients with various other solid tumors were treated with combination chemotherapy consisting of DTIC, at a fixed dose, with either adriamycin, CCNU, or hydroxyurea, at several dosages. An objective response rate of 20% was observed in 84 evaluable melanoma patients. The addition of the other agents to DTIC did not provide enhanced antitumor activity. Combination chemotherapy increased toxicity. Encouraging objective responses were observed in patients with synovial sarcoma (4/7) and teratocarcinoma of the testis (1/1) treated with the combination of adriamycin and DTIC.

Clinical Trials as Topic↗

Combination chemotherapy with CCNU (NSC-79037),hexamethylmelamine (NSC-13875) and methotrexate (NSC-740) in advanced bronchogenic carcinoma.

18 patients with metastatic or recurrent bronchogenic carcinoma and one patient with a squamous cell carcinoma of the trachea were treated with a combination of CCNU, hexamethylmelamine and methotrexate. Objective remissions were observed in 3/19 (16%): 1 complete, 1 partial (greater than 50%) and 1 incomplete (less than 50%). However, the patient with the complete response was the only drug death, on day 21. Remission duration in the other two patients was 3 and 9+ months respectively. One patient with oat cell carcinoma experienced no tumor progression for 5 months. This combination resulted in severe gastrointestinal toxicity in 5/19, severe thrombopenia in 12/19 and severe neutropenia in 6/19. We conclude that the combination as used here resulted in no increased clinical effectiveness and proved to be quite toxic.

Aged↗

Nitrosourea combination chemotherapy: 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (methyl-CCNU) and cyclophosphamide.

MCCNU and cyclophosphamide are synergistic in animal tumor systems and have different chronology patterns for dose-limiting myelosuppression. The combination was employed in 49 patients with metastatic cancer with each drug administered on successive days and repeated at 6-week intervals. A total of 108 courses of therapy were monitored, and leukopenia (WBC less than 3,000 cells/mm3) and thrombocytopenia (platelets less than 150,000/mm3) were observed in 47 and 30%, respectively, at nadir days 15 and 22. No clinically beneficial effects were observed in 40 patients with measurable disease. Combination chemotherapy employing nitrosoureas have not, as in this study, generally demonstrated synergistic therapeutic effects possibly related to the low level of antitumor activity of nitrosoureas in solid tumors and the use of suboptimal doses for one of more agents in the combination.

Adult↗

The efficacy of 5-fluorouracil, mitomycin C, and methyl CCNU in advanced gastrointestinal malignancy.

50 patients with advanced gastrointestinal malignancies were treated with 5-fluorouracil (5FU), 1-(2-chloroethyl)3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and mitomycin C (Mito C). 43 patients, with diagnoses of colorectal, pancreatic or gastric cancer, were evaluable. 13 patients (30%) achieved complete remissions, and 4 achieved partial remissions. The median durations of responses in colorectal, pancreatic and gastric disease were 11.0, 11.0, and 11.5 months, respectively. Survival was definitely prolonged in responding patients with pancreatic and gastric carcinomas. The combination was well tolerated. Mucositis, leukopenia, and thrombocytopenia were the major toxicities that occurred. The quality of life was improved in all responding patients.

Adenocarcinoma↗

Acute leukemia following combination chemotherapy for cancer of the lung.

A 64-year-old male with recurrent metastatic squamous cell carcinoma was successfully treated with intensive combination chemotherapy. His complete remission was maintained with a nitrosourea, nitrogen mustard and methotrexate for 3 years. While in remission the patient developed acute leukemia. It appears that this secondary malignancy was due to his prolonged chemotherapy.

Antineoplastic Agents↗

Ultrastructural changes in HeLa cells following treatment with the antineoplastic agent cis-acid.

The ultrastructure of HeLa cells arrested in the G2 phase of the cell cycle by the antineoplastic agent cis-acid was studied and compared with that of normal G2-phase-synchronized cells. The results demonstrate that the chromatin of drug-treated cells was fragmented and clumped, the membranous structures had degenerated or were destroyed and the polyribosomes were decreased. The mitochondria were swollen and vacuolated, suggesting that energy production might have been impaired.

Cell Cycle↗

Procarbazine, CCNU and vincristine (PCV) combination chemotherapy for brain tumors.

12 patients with brain tumors were treated with a combination of procarbazine, CCNU (bis-2-chloroethyl-3-cyclohexyl-1-nitrosourea) and vincristine. 3 of 8 patients (37.5%) with primary brain tumors responded to chemotherapy, with a mean duration of 9.3 months. The mean survival of responders was 11.7 months, versus 3.6 months for nonresponders. 4 patients with metastatic brain tumors were also treated with the same combination chemotherapy; only 1, suffering from a lymphoma of the brain, responded partially.

Adult↗