Effect of the degree of nodularity on the survival of patients with nodular lymphomas.

The survival of patients with favorable lymphoma entered on various Eastern Cooperative Oncology Group (ECOG) studies was analyzed according to the degree of nodularity. A pure nodular pattern (NN), defined as nodularity involving 75% or more of the cross-sectional area, was found to be an important favorable prognostic indicator as compared with a nodular-diffuse pattern (ND). The median survival in 336 patients with NN of 68.2 months was significantly better than the 39.6 months in 87 patients with ND (P less than .003). The median survival in NN-lymphocytic poorly differentiated (LPD) was 77.2 months v 44.3 months for ND-LPD. NN-M median survival of 56.4 months contrasted with only 25.5 months for ND-mixed lymphocytic and histiocytic (M). The degree of nodularity as defined in this study appears to have significant prognostic implication and should be more widely used by pathologists.

Sequential cyclophosphamide-prednisone and vincristine-bleomycin (CPOB). An effective, schedule-dependent treatment for advanced diffuse histiocytic lymphoma.

In an Eastern Cooperative Oncology Group non-Hodgkin's lymphoma clinical trial, 90 patients with Stage III or IV diffuse histiocytic lymphoma (DHL) were treated with one of four chemotherapy regimens. All patients were previously untreated with chemotherapy, and careful restaging was required to document responses. Each treatment included cyclophosphamide, vincristine and prednisone (COP) plus Adriamycin (COPA), BCNU (BCVP) or bleomycin (COPB and CPOB). The two bleomycin-containing regimens differed only in the schedule of drug administration. CPOB-treated patients received cyclophosphamide on day 1, prednisone on days 1 to 5 and vincristine and bleomycin on day 15 of each 21-day cycle. COPB-treated patients received the same four drugs in the same dosage; however, the schedule was changed so that vincristine and bleomycin were given on day 1. Treatment of responders was continued for 8 cycles. Those with a complete response (CR) were randomized to maintenance therapy with BCVP or no treatment. Treatment with CPOB yielded a CR rate of 55% compared to 25% for COPB (P = 0.07). In contrast to COPB, treatment with CPOB was associated with a significantly longer median duration of CR (26.5 versus 5.7 months; P less than 0.05) and median survival (27.7 versus 11.2 months; P less than 0.02). The CR rate was 31% for BCVP and 45% for COPA, and the median survivals were 10.7 months and 14.4 months, respectively. One half of the CPOB-treated patients who achieved CR remained alive in continuous CR after 30 to 72 months. No advantage for maintenance therapy was observed. Myelotoxicity was greater with CPOB than COPB, but comparable to COPA. This trial demonstrated that the results of treatment of DHL with COP plus bleomycin were strikingly dependent upon the schedule of administration of bleomycin and vincristine. Bleomycin effectively combined with COP, as in CPOB, yielded results comparable to those obtained when Adriamycin was added to COP. CPOB appears to be an effective treatment for DHL that should be considered as an alternative to other regimens, particularly for patients who cannot receive Adriamycin.

Moderate versus intensive chemotherapy of prognostically favorable non-Hodgkin's lymphoma: a progress report.

Two hundred and fifty-two patients with advanced stages of favorable non-Hodgkin's lymphoma (NHL) subtypes (nodular histiocytic (NH), and diffuse well-differentiated lymphocytic (DLWD)) were analyzed for response and survival to moderate (cyclophosphamide-prednisone (CP)) vs. intensive (BCVP or COPP) chemotherapy regimens. The overall complete response (CR) rate was 57%. The median duration of remission for the entire group was 88 weeks and 65% of complete responders were in remission at one year. Survival rates at one year were 87% for BCVP, 86% for COPP, and 91% for CP. The response rate, response duration, and survival rate differences between the groups were not significant. Severe and life threatening hematologic toxicity rates were significantly higher with BCVP and COPP as compared to CP (P less than 0.001). The highest CR rate was obtained in NM (74%) and CP gave the highest CR rate in DLWD (60%). Survival rates at one year for NM (97%) and NLPD (90%) were comparable whereas the one-year survival rate for DLWD was significantly lower (75%) than that for NLPD (P less than 0.005) or NM (P less than 0.001). We conclude that in favorable NHL subtypes, cyclophosphamide-prednisone combination is an effective regimen with minimal toxicity.

Nodular mixed lymphocytic-histiocytic lymphoma (NM): response and survival. Eastern Cooperative Oncology Group.

Eighty patients with nodular mixed lymphocytic-histiocytic lymphoma (NM) entered on four different Eastern Cooperative Oncology Group chemotherapy studies were analyzed for response and survival. They were compared with 249 patients with nodular lymphocytic poorly differentiated lymphoma (NLPD), who were treated similarly. The response rates in NM were: CR 45%, PR 30%, NC-PD 25%. In NLPD the quality of response had little effect on survival (CR 91%, PR 90%, NC-PD 76%), whereas in NM the two year survivorship of 85% for CR dropped drastically to 33% for the partial responders (P less than 0.01). Ninety percent of the previously untreated NLPD, but only 59% of the comparable group of NM, survived 2 years. In 23 patients with NM in which the pattern was reported as both nodular and diffuse (ND-M), the 2-year survival of 35% was markedly inferior to a 66% 2-year survivorship observed in 57 patients with the pure nodular pattern (P less than 0.05). It appears that NM is a less favorable lymphoma type than NLPD. In NM achievement of a CR affects survival favorably; consequently, the use of aggressive chemotherapy regimens in an attempt to achieve high rates of CR are recommended. In NLPD, on the other hand, since survival curves of partial and complete responders are almost identical, suboptimal treatments may be justified.

Results of a randomized study comparing DTIC with TIC mustard in malignant melanoma.

This prospective randomized Eastern Cooperative Oncology Group (ECOG) study (1071) was designed to compare a new and promising cytotoxic agent TIC Mustard (triazeno imidazole carboxamide mustard, NSC 82196) with DTIC (dimethyl triazeno imidazole carboxamide, NSC 45388) in the treatment of inoperable melanoma. One hundred and seventy-eight patients were randomized to receive either DTIC (150 mg/m2/day X 5) or TIC Mustard (800 mg/m2/day X 5). Of this group 145 patients were evaluable for tumor response at the completion of the study. Objective responses were seen in 15/79 (19.0%) DTIC patients and 4/66 (6.1%) TIC Mustard patients. Adjustment of crude response rates yielded final response rates of 18.2% for DTIC patients and 5.8% for TIC Mustard. These differences were significant at the p less than or equal to .03 level. Median response duration was 15 weeks for the DTIC responders and 4 weeks for the TIC Mustard responders. Responders and nonresponders did not differ significantly in any of the standard prognostic categories. However, responders had a significantly longer median survival (47.5 weeks) compared to that for nonresponders (17.8 weeks). Toxicity was tolerable for either drug and no deaths were ascribed to either. We conclude that TIC Mustard has limited usefulness in the treatment of malignant melanoma and is less effective than DTIC.