Combination chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone (VEPA) for non-Hodgkin's lymphoma

Combination Chemotherapy with Adriamycin (VEPA) was applied to 16 patients with non-Hodgkin's lymphoma. The effects of VEPA therapy were compared with those of combination chemotherapy without Adriamycin (non-VEPA). Complete remission rate achieved with VEPA therapy was 37.5% while that with non-VEPA therapy was 27.6%. Histologically, the complete remission rate in cases of large-cell type treated with VEPA therapy was 40%, while that with non-VEPA therapy was 14.3%. No cases of stage IV showed complete remission, whereas the complete remission rate for cases of stage III was 37.5% for VEPA therapy, but 27.6% for non-VEPA therapy. From these results we concluded that VEPA therapy is more effective for non-Hodgkin's lymphoma, especially large-cell type, than non-VEPA therapy.     

Combination chemotherapy with pirarubicin (THP), cyclophosphamide, vincristine, and prednisolone (VEP-THP therapy) in the treatment of non-Hodgkin's lymphoma

Twenty-eight patients with non-Hodgkin's lymphoma (NHL) were treated with a combination of (2'-R)-4'-o-tetrahydropyranyladriamycin (pirarubicin, THP), cyclophosphamide, vincristine, and prednisolone (VEP-THP therapy). Eleven (45.8%) of twenty-four evaluable patients achieved complete response (CR). CR rate (52.8%) was higher in the intermediate-grade histology group than in high- or low-grade group. Toxicity was generally acceptable although leukopenia less than 2,000/microliters was observed in 17 (60.7%) of 28 patients. Clinical signs of cardiotoxicity were not observed and alopecia was mild. Therefore, VEP-THP therapy is useful as a first-line chemotherapy in the treatment of NHL, particularly for the patients with intermediate-grade histology. Higher CR rate and longer relapse-free survival can be expected by administering a greater dose of THP or employing a schedule of fractionated low doses.     

Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP).

Twenty-three patients with diffuse histiocytic lymphoma who had not had prior chemotherapy were treated with CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone). Sixteen of these patients had previously been treated with radiation therapy. Nine of these 23 patients had a pathologically documented complete response at the conclusion of CHOP with an overall complete response rate of 39%. In patients whose disease was confined to lymph nodes, the complete response rate was 7 of 8 or 88%, while in patients with stage IV disease, only 2 of 15 or 13% had complete responses. Although prior radiation therapy could not be demonstrated to be an adverse prognostic factor in this small series, it could have accounted for the low overall complete response rate noted. Complete response in this series was well sustained with an actuarial relapse-free survival of 75% and an actuarial survival of 89% at two years. No complete responses occurred in five patients who had received prior chemotherapy.     

Combination chemotherapy of metastatic breast cancer with vincristine adriamycin and prednisolone

Fifty patients with metastatic breast cancer were treated with a combination of vincristine, Adriamycin and prednisolone (VAP) at four weekly intervals. Response rates of 78% for soft tissue disease, 66% for parenchymal lung disease, 67% for liver disease, and 64% for pleural effusions were seen. Only 26% of patients with bone metastases showed an objective response. These figures are as good as any previously reported for chemotherapy of breast cancer.     

Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in advanced non-Hodgkin's lymphomas.

From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival.     

Combination chemotherapy with cyclophosphamide, adriamycin, and vincristine in malignant thymoma and myasthenia gravis

Malignant thymoma (MT) is a rare tumor that is often associated with myasthenia gravis (MG). This tumor is considered resistant to chemotherapy. We had the opportunity to treat five patients with MT with cyclophosphamide 800 mg/m2, Adriamycin 50 mg/m2, and vincristine 1.4 mg/m2 (CAV) in cycles of 21 days. Two patients with MG that was resistant to antimyasthenic drugs immediately responded to this combination. One patient with only MT had a complete response, and two patients with only MT had a partial response. Two out of the five patients are still alive and free of disease. Two patients died of disease, and one died from a neutropenia-induced respiratory tract infection. It is concluded that this combination chemotherapy is active in MT and MG and deserves additional trials.     

Combination chemotherapy (vincristine, adriamycin, cyclophosphamide, and 5-fluorouracil) in the treatment of children with malignant hepatoma

Members of Childrens Cancer Study Group and the Pediatric Division of the Southwest Oncology Group conducted a study of chemotherapy for children with malignant liver tumors. All patients received vincristine, cyclophosphamide, Adriamycin and 5-fluorouracil in 6 weekly cycles for one year. Surgical resection and irradiation were employed when indicated. Between January 1976 and August 1978, 62 patients were entered on study; one was rejected for a protocol error, and ten had inadequate trials of chemotherapy, dying within one month of entry. The median time on study for all patients was 12 months. Twenty-four patients had no measurable disease following surgical treatment and chemotherapy was employed as adjuvant treatment; 20/24 (83%) remain relapse-free from 8-42+ months, (median, 30 months). In 27 patients, residual measurable disease was available to determine the response to chemotherapy. The response rate was 12/27 (44%), lasting 3-45 months (median, 18 months). The median follow-up of all survivors is 30 months. Hematologic toxicity was significant, particularly during the initial courses of chemotherapy; 28/57 patients developed severe toxicity which was fatal in three. The results from the current study were compared to those from a previous one initiated in 1972, in which actinomycin D, vincristine, and cyclophosphamide were given in sequence, one during each month for one year. Although the population of the two studies was not identical, there was a difference in the response rates (P = 0.02), relapse-free interval (P = 0.008), and survival (P = 0.003). The most striking improvement was seen in the patients with Group I disease, there were 7/11 relapses in the first study and 1/16 in the current one.     

Combination chemotherapy with irinotecan and adriamycin for refractory and relapsed non-Hodgkin's lymphoma

Twenty-five patients with relapsed or refractory non-Hodgkin's lymphomawere treated by combination chemotherapy with irinotecan hydrochloride(CPT-11) and adriamycin (ADM): CPT-11, 25 mg/m² on days 1 and 2;ADM, 40 mg/m² on day 3. Nine (36%) of twenty-five patientsachieved CR. Fairly good responses were seen in relapsed B-cell lymphomas (4of 8 in diffuse large B-cell lymphoma and 2 of 2 in follicular lymphoma grade1), and substantial responses in T-cell lymphomas (1 of 4 in peripheral T-celllymphoma and 2 of 7 in adult T-cell leukemia/lymphoma). Leukopenia wasfrequent but tolerable, and diarrhea minimal. Combination chemotherapy witha reduced dose CPT-11 and ADM was useful in the treatment of relapsednon-Hodgkin's lymphoma.     

CAP (cyclophosphamide,adriamycin, platinum) vs CMFVP (cyclophosphamide,methotrexate, 5-fluorouracil,vincristine, prednisolone) combination chemotherapy in untreated metastatic breast cancer

Summary The prospective controlled phase III clinical trial compared the therapeutic value of the cis-platinum — adriamycin — cyclophosphamide combination (CAP) and that of the combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisolone (CMFVP) in untreated metastatic breast cancer. Seventy-two patients (>2 cycles) were evaluated: 36 had received CAP and 36, CMFVP. An objective response (CR+PR) to CAP combination chemotherapy was achieved in 75% of patients (27 of 36), with a high rate (42%) of complete remissions. In terms of metastatic site, the response rate appeared to be particularly high in soft tissue and visceral organ (lung, liver) metastases. In the CMFVP group, an objective response was noted in 16 of 36 patients (44%) with 19% complete remissions. Overall therapeutic response and the complete remission rate were better with CAP regimen (statistically significant; P<0.01). The duration of remissions was 4–16+months (M=12) for CAP and 2–12+months (M=8) for CMFVP. Toxic side-effects were more pronounced in the CAP group, particularly myelosuppression, and anemia was prevalent. Side-effects of CMFVP treatment were mild. In 11 CMFVP-resistant cases CAP was administered as second-line treatment, and an objective response was observed in 45% of cases (5 of 11). The preliminary results of this controlled trial show the advantage of the CAP combination in the treatment of metastatic breast cances.     

The combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation

The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. CHOP was given in the following manner: cyclophosphamide 400 mg/M2 IV day 1, adriamycin 40 mg/M2 IV day 1, vincristine 2 mg IV day 1, and Prednisone 100 mg po daily X 5. Forty-five rad total body irradiation was delivered in three fractions on days 21, 23 and 25. Chemotherapy was repeated on day 42, etc., until four cycles of CHOP and three cycles TBI (135R) were delivered. Responses were seen in 8/11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. Two of the living patients are alive with disease and the remainder are in unmaintained remission. Two persons died with no response and one died in complete remission of an unrelated illness. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3,020 X 10(9)/microliters (range 1.2-5.5) and a mean nadir platelet count of 188 X 10(9)/microliters (range 016-270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients.     

Results of combined chemotherapy of lymphosarcoma with cyclophosphamide, vincristine and prednisolone

The effectiveness of treatment of lymphosarcoma of lymph nodes with cyclophosphamide, vincristin (oncovin) and prednisolone (scheme COP) was found to depend on the cytomorphological type of tumor, stage and previous therapy, with duration of remission being in direct correlationship with its degree.     

Combination chemo-endocrine therapy of metastatic and stage IV breast cancer with cyclophosphamide, adriamycin, prednisolone and tamoxifen (CAPT)--with special reference to management of brain and liver metastasis

Sixty-three evaluable patients with metastatic and stage IV breast cancer who had not previously undergone chemo-endocrine therapy were treated with a combination chemoendocrine therapy regimen consisting of cyclophosphamide 100 mg p.o. every day, adriamycin 10 mg i.v. on day 1 to 5, prednisolone 10 mg or 20 mg (20 mg was given on day 1 to 5) p.o. every day, and tamoxifen 20 mg p.o. every day. Adriamycin on day 1 to 5 was repeated three times every two weeks. After a total dose of 150 mg of adriamycin, the patients were changed to maintenance therapy consisting of cyclophosphamide 100 mg p.o., prednisolone 10 mg p.o. and tamoxifen 20 mg p.o. every day. After 72 months of the treatment there were 61 patients good for evaluation, 13 patients achieved a complete response (21.3%) with a median survival of 30.5 months and 18 patients had a partial response (29.5%) with a median survival of 21.0 months, and 30 patients failed to respond (49.2%) with a median survival of 8.5 months. There was a significant difference in survival time between responders (CR + PR) and non-responders (NC + PD) (p less than 0.001). Responses by site were seen in lung 10/18 (55.6%), liver 3/6 (50.0%), brain 2/4 (50.0%), bone 6/17 (35.3%) and soft tissue 14/24 (56.3%). A Satisfactory response for brain and liver metastasis, which are usually viewed as a sign of grim prognosis, was obtained similar to other sites of metastasis. Retreatment with CAPT, which was attempted in patients with secondary brain metastasis who responded to CAPT for initial brain metastasis, was uniformly effective. High ration of androgen to corticosteroid, positive estrogen receptors, long disease-free survival (over two years), premenopausal, high Broca' index (above 110) resulted from the chemo-endocrine therapy regimen CAPT. Toxicity was minimal and consisted of nausea, vomiting, alopecia and leucopenia.     

A retrospective analysis of combination chemotherapy consisting cyclophosphamide,vincristine, prednisolone and procarbazine (C-MOPP) for pretreated aggressive non-Hodgkin lymphoma

The C-MOPP regimen, consisting cyclophosphamide, vincristine, prednisolone and procarbazine, has been used for treatment of non-Hodgkin lymphoma; however, there are few reports of this therapy against aggressive lymphoma. We performed a retrospective analysis of previously treated 89 patients who had received C-MOPP therapy from 1999 to 2013 at our institution. Median age was 67 (range, 22–81) years. Twenty-eight patients obtained CR, 5 obtained PR, and overall response rate was 37% (33/89). The estimated 1-year overall survival and progression-free survival rates were 61 and 33%, respectively. Major grade > 2 toxicities were leucopenia (55%) and neutropenia (52%). Efficacy and toxicity were in line with other recent studies involving new agents, given that the subjects mainly consisted of elderly outpatients. These data provide a rationale for the use of C-MOPP as a current control treatment arm when the response to new cancer therapy agents is evaluated.     

The effects of multiple combination chemotherapy with vincristine,cyclophosphamide (Endoxan), methotrexate, 5-fluorouracil,adriamycin and prednisolone (VEMFAH) for advanced breast cancer

Thirty-eight patients with advanced breast cancer were treated with the 'VEMFAH' multiple-drug combination chemotherapy, consisting of vincristine (V), cyclophosphamide (Endoxan; E), methotrexate (M), 5-fluorouracil (F), adriamycin (A), and prednisolone (H). Disease response was evaluated by the UICC criteria. Among the 35 evaluable cases, 4 complete responses (CR), 23 partial responses (PR), 2 cases of no change (NC), and 6 of progressive disease (PD) were observed. The response rate (CR + PR) was 77.1%. The median duration of response was 52 weeks (8-192 weeks) or 12 months. In 32 patients who received more than two courses of therapy the 50% survival time of responders was 27.0 months, which was significantly longer than the 10.3 months of nonresponders (P less than 0.05). Except for 2 patients who developed myocardial damage, the therapy was never terminated because of side effects. Cumulative cardiotoxicity was not apparent in this study. This multiple-drug combination chemotherapy with 'VEMFAH' is concluded to be an effective treatment for advanced and disseminated breast cancer.     

Combination chemotherapy with cyclophosphamide,vincristine, procarbazine,and prednisone (COPP) in children with brain tumors

Summary The chemotherapeutic combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) was used to treat 15 children with recurrent central nervous system tumors and seven children with newly diagnosed brainstem tumors. In patients with recurrent tumors, marginal activity was seen in various histologic types. COPP chemotherapy was clearly ineffective in patients with brainstem tumors. Toxicity consisted of mild to moderate myelosuppression and neurotoxicity.     

Combination chemotherapy (modified CHOP-Bleo) in non-Hodgkin's lymphoma]

Twenty-six adults with advanced non-Hodgkin's lymphoma (73% in clinical stage IV) were treated with a combination of cyclophosphamide, hydroxyldaunorubicin, vincristine, prednisolone and bleomycin (modified CHOP-Bleo), from May 1978 to July 1987. Complete remission (CR) was obtained in 12 of 26 patients (46%). The median survival time was 19.5 months (2-77 + months), Median duration of CR was 30.5 months (2-76 + months). The survival of patients with diffuse lymphoma large cell type (DL) was better than those with other diffuse lymphomas. The 50% of patients with DL are projected to be free of disease. The survival of patients with clinical stage III was significantly better than those with clinical stage IV. Major complications during chemotherapy with modified CHOP-Bleo were myelosuppression, constipation and peripheral neuropathy. These toxicities were generally mild and well tolerated.     

VAC (vincristine,adriamycin, cyclophosphamide) chemotherapy for metastatic carcinoma from an unknown primary site

Twenty patients presenting with metastatic carcinoma from an unknown primary site were studied. All patients were treated with a triple chemotherapy regimen of vincristine, adriamycin and cyclophosphamide repeated at three-week intervals. The response rate was 50%, and the four patients achieving complete response are alive and disease-free at 13, 16, 36 and 39 months. Toxicity was minimal and the majority of patients' performance status improved with the chemotherapy. VAC chemotherapy is indicated for patients with metastases, particularly of soft tissues originating from a carcinoma from an unknown primary site.     

Combination chemotherapy with mitomycin C, methotrexate, and vincristine (MMV) for metastatic breast cancer refractory to adriamycin

Twenty-five patients with metastatic breast cancer who had failed with combination chemotherapies including adriamycin were treated with a combination of mitomycin C, methotrexate, and vincristine (MMV). MMC 5 mg/m2, methotrexate 18 mg/m2, vincristine 0.7 mg/m2 were given i.v. on days 1 and 8, and repeated every 21 days. Seven patients (28%) experienced a partial response: 7 maintained NC and 11 failed to respond (PD). Median duration of regression was 12 weeks. Median survival time in PR patients was one year and 3 months, contrary to 6 months in patients with NC or PD. This combination was well tolerated except thrombocytopenia in 5 patients.