Variables contributing to anticipatory nausea and vomiting in cancer chemotherapy.

Forty cancer patients receiving parenteral chemotherapy were assessed for characteristics associated with the development of anticipatory nausea and vomiting (ANV). The patients who developed ANV were more likely to have increased pretreatment anxiety (p less than 0.05), greater posttreatment dizziness/lightheadedness (p less than 0.01), more severe postchemotherapy vomiting (p less than 0.01), and a delayed onset of postchemotherapy nausea and vomiting (PCNV) compared to the patients who developed neither ANV nor PCNV. However, when patients who did not develop PCNV were excluded from the analysis, the difference between the ANV and non-ANV patients remained significant only for postchemotherapy dizziness/lightheadedness (p less than 0.05). In an attempt to identify a group of variables that better predict the development of ANV, we analyzed the data for combinations of variables. Two indices were found to correctly classify ANV and non-ANV patients 71% of the time (p less than 0.05). Index A refers to the presence of at least two of the following variables, pretreatment anxiety, posttreatment dizziness/lightheadedness, and latency of PCNV. Index B refers to the presence of at least two of the following variables: pretreatment anxiety, severity of nausea, and severity of vomiting. The identification of characteristics associated with the development of ANV could lead to new intervention strategies.

A pilot study of the Functional Living Index-Cancer (FLIC) Scale for the assessment of quality of life for metastatic lung cancer patients. An Eastern Cooperative Oncology Group study.

Quality of life is an important factor in the assessment of cancer therapy, but it is difficult to define and measure. The Functional Living Index-Cancer (FLIC) was designed specifically for cancer patients under treatment. The Eastern Cooperative Oncology Group (ECOG) mounted a pilot study to assess the feasibility and sensitivity of the patient-oriented FLIC scale for assessment of quality of life. The results of this study show that the FLIC scores correlate with the functional status of patients on treatment: high scores on the FLIC prior to therapy were found to correlate with good performance status (p = 0.0001), and decreases in the FLIC score during therapy correlated with a decline in performance status (p = 0.0001), with poor performance status (p = 0.0002), and greater than 5% recent weight loss (p = 0.004). However, there was poor compliance to completion of the instrument, indicating a need for future research into this aspect of assessing quality of life in the cooperative group setting.

Fulminant leukemic polyradiculoneuropathy in a case of B-cell prolymphocytic leukemia. A clinicopathologic report.

A 52 year old man with a 10-month history of B-cell prolymphocytic leukemia (PLL) died of an apparent acute fulminant polyradiculoneuropathy, a condition generally attributed to paraneoplastic complication. The pathologic examination disclosed diffuse leukemic infiltrations of the peripheral nervous system. It is suggested that this particularly aggressive form of B-cell chronic prolymphocytic leukemia presented a constellation of features that promoted the invasion of the peripheral nervous system by way of the bloodstream and may explain the unusual clinical presentation.

The effect of intensive intermittent maintenance therapy in advanced low-grade non-Hodgkin's lymphoma.

One hundred and eleven patients with low-grade histology non-Hodgkin's lymphoma achieving a restaged complete response to one of three induction therapies on Eastern Cooperative Oncology Group (ECOG) protocol EST 2474 were randomized to receive either maintenance treatment with BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) given every 6 weeks for an additional 18 months or no further therapy. Overall toxicity was moderate. The median progression-free survival (PFS) on maintenance therapy was 3.2 years versus 2.0 years for those observed without treatment (P = 0.02). Progression-free survival was significantly shorter for patients with nodular and diffuse pattern (ND), histiocytic or mixed histology compared with pure nodular lymphocytic, or poorly differentiated counterpart (P = 0.0007), thus confirming the prognostic significance of histologic subtypes. However, the overall survival of patients was not improved by maintenance treatment, suggesting that therapy upon relapse was an equally effective alternative clinical strategy.

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.

Simultaneous cloacogenic carcinoma in dizygotic twins.

Dizygotic twins developed cloacogenic carcinoma of the anus almost simultaneously. The patients, although separated from the time they were 20-years-old, had very similar life styles. There are several reports in the medical literature of synchronous tumors in mono and dizygotic twins. It is recommended that if a cancer diagnosis is made in one twin, the other undergo workup to exclude the presence of a tumor with similar histology. The establishment of state or national twin registries would provide valuable information regarding the role of genetic and environmental factors in the development of not only cancer but also of various nonmalignant disorders.

Anxiety levels in patients randomized to adjuvant therapy versus observation for early breast cancer.

We studied anxiety levels in 68 patients who had been randomized to adjuvant chemotherapy v observation on two Eastern Cooperative Oncology Group (ECOG) protocols. All subjects were women who had undergone total or modified radical mastectomy for breast cancer. Immediately before breast protocol randomization and again 3, 6, and 12 months later, patients completed two self-report measures: the State-Trait Anxiety Inventory and the SCL-90. There were no consistent trends in anxiety levels over time. At each test point, patients under observation displayed higher anxiety scores than did patients receiving adjuvant therapy, but these differences failed to attain statistical significance. Power calculations indicate that these results rule out the possibility of major differences in anxiety levels among patients randomized to observation v adjuvant therapy, but a larger patient sample is required before a definitive statement can be made about smaller differences.

Hypogammaglobulinemia and hemophagocytic syndrome associated with lymphoproliferative disorders.

Four patients with lymphohistiocytic disorders had or subsequently experienced severe hypogammaglobulinemia and pancytopenia due to hemophagocytosis. The percentages of B- and T-lymphocytes and the ratios of helper (OKT4) cells to suppressor (OKT8) cells in the peripheral blood were variably altered. Mitogenic response to pokeweed mitogen and phytohemagglutinin was depressed but could be restored to near normal by the in vitro addition of indomethacin or interleukin-2. The half-life of intravenously administered immunoglobulin was markedly shortened. The data indicate that hyperactive monocytes/histiocytes are capable of simultaneously ingesting apparently normal blood cells and immunoglobulin, leading to pancytopenia and hypogammaglobulinemia. The monocytes with suppressor activity (which could be abrogated with indomethacin or interleukin-2) appeared to additionally contribute to the hypogammaglobulinemia, possibly by interfering with the terminal differentiation of the B-lymphocytes. Hemophagocytosis occurs frequently in histiocytic and occasionally in lymphoproliferative disorders or viral diseases. More frequent and serial determination of serum immunoglobulin levels in such situations may lead to the discovery of additional cases.

Moderate versus aggressive chemotherapy of nodular lymphocytic poorly differentiated lymphoma.

One hundred twenty-eight patients with purely nodular lymphocytic poorly differentiated lymphoma (NLPDL) without any prior therapy, entered on Eastern Cooperative Oncology Group protocol EST 2474, were analyzed for response, progression-free and overall survival. The restaged complete response rates with cyclophosphamide-prednisone (CP) (moderate regimen) of 54% compared favorably with those of the more intensive regimens; cyclophosphamide, vincristine, procarbazine and prednisone (COPP) (56%) and BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) (53%). The toxicity of the regimens decreased from BCVP to COPP to CP. The median survival rate for the entire group was 7.8 years. Estimated progression-free survival at five years by regimen was COPP, 57%; BCVP, 26%; CP, 22% (P = .02). No other prognostic parameter significantly affected progression-free survival. In spite of the better progression-free survival of COPP-treated patients, the overall survival rates with the different induction regimens were similar. Maintenance therapy for patients in complete response at the end of induction therapy with periodic BCVP reinduction did not significantly affect the disease-free or overall survival. Cyclophosphamide-prednisone is a minimally toxic regimen effective in the treatment of NLPDL, but COPP, in view of its acceptable toxicity in this patient population and apparent superiority in providing a longer disease-free state, deserves further testing.

T-suppressor cell chronic lymphocytic leukemia. Phenotypic characterization by monoclonal antibodies.

A patient with long standing seropositive rheumatoid arthritis developed lymphocytosis which phenotypically involved the cytotoxic/suppressor T-lymphocyte population. There are 10 reported instances of this new disease entity described as "chronic T-cell lymphocytosis with neutropenia" or "chronic suppressor T-cell lymphocytic leukemia." The disease is characterized by hepatosplenomegaly, neutropenia, and the frequent presence of rheumatoid factor without clinical evidence of rheumatoid arthritis. Splenectomy in our patient, as well as in other instances where undertaken, has been ineffective in alleviating the neutropenia. The peripheral blood lymphocytes in our patient were OKT-3+, OKT-5+, OKT-8+, OKT-11+, cALL-, OKT-6-, TdT-. They possessed ADCC but no NK activity and did not suppress PWM-induced B-cell differentiation in spite of the presence of Fc receptor for IgG. Since the lymphocytosis of OKT-8+ cells appears to be clonal, it is suggested that the disease be designated chronic suppressor T-cell lymphocytic leukemia.

B-lymphoproliferative disorders: a proposed unified pathogenetic pathway.

The clinical features of lymphoproliferative diseases associated with paraproteinemia are briefly reviewed and correlated with current immunologic concepts in an effort to clarify the pathophysiology of B-lymphocyte disorders. B-lymphocyte maturation proceeds in a predictable manner from the Pre-B cell to the formation of idiotype specific plasma cells and memory B-lymphocytes. The immunoglobulin isotype produced by the mature plasma cell is determined by a site specific process of gene switching which proceeds from mu to alpha production. Lymphoproliferative diseases are the result of disordered B cell maturation and their clinical features can be explained by identifying the locus of the maturational defect.

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.

Pulmonary scar carcinoma. A clinicopathologic analysis.

To delineate differences between scar and non-scar pulmonary carcinoma, the charts, autopsy protocols and chest roentgenograms of 80 male patients (autopsied) between 1975 and 1980, were reviewed. Nineteen patients (24%) had documented scar carcinomas. The comparison revealed scar carcinomas to possess certain distinctive features: A higher histologic distribution of adenocarcinoma (58% versus 15% in non-scars) and the frequent presentation (53%) with only nonpulmonary symptoms and signs related to metastasis. In scar carcinomas both bronchoscopy and sputum cytology were ineffective as initial diagnostic tools since chest findings were absent or minimal. Chest x-ray was negative in 9 of the 19 patients with scar cancer and remained negative until death in seven. In 10 of 19 instances, pulmonary scar carcinomas presented with only nonpulmonary symptoms and showed a tendency to metastasize while clinically undetectable. The differences noted between scar and non-scar carcinomas of the lung appear to depend on the peripheral location of these tumors and not on the adenocarcinoma histology.

Rosette and blastogenesis inhibition by plasma from Hodgkin's disease and other malignancies. Positive correlation in State I and II Hodgkin's disease.

The simultaneous presence of both rosette- and mitogen-induced blastogenesis inhibitors was measured in the plasma from 29 patients with active Hodgkin's disease, 21 patients with advanced lung cancer, nine patients with diffuse histiocytic lymphoma, 25 patients with non-Hodgkin's lymphoma, and 17 patients with a variety of solid tumors. Only patients with active Hodgkin's disease consistently demonstrated factors which interfered with both rosetting and mitogenesis when normal allogeneic cells were utilized. While a similar proportion of patients with early and late Hodgkin's disease possessed plasma which could inhibit both tests, a significant correlation between these tests was observed only in Stage I and II disease. Varying degrees of inhibition of these tests was also observed when plasmas from patients with other malignancies were tested. Both lung cancer and histiocytic lymphoma plasma contained a factor which was capable of significantly inhibiting in the rosette assay when compared to normal human serum. Plasma from these patients also demonstrated inhibition of blastogenesis, but unlike Hodgkin's disease, no correlation between these activities could be demonstrated. Neither patients with diffuse or nodular lymphocytic lymphoma nor patients with solid tumors had significant plasma inhibition in either assay.

Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy.

Fifty-two patients with stage III or IV nodular mixed lymphocytic-histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3-4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.

Chemotherapy of advanced esophageal carcinoma: Eastern Cooperative Oncology Group experience.

In a Phase II study, patients with measurable metastatic or recurrent esophageal carcinoma randomly received after Adriamycin (ADR), 60 mg/M2 I.V. q three weeks, or methotrexate (MTX), 40 mg/M2 I.V. q one week, or 5-fluorouracil (5-FU), 500 mg/m2 I.V. x 5 days q five weeks. Objective partial response rates for 72 patients were 5% for ADR (one of 20), 12% for MTX (three of 26), and 15% for 5-FU (four of 26). There were no complete responses. Median duration of response was 13 weeks. Median survival was 14 weeks (eight weeks for ADR, 14 weeks for MTX, and 15 weeks for 5-FU). Factors of liver metastasis, adjacent anatomic involvement, time from initial diagnosis to study entry, and prior radiation were found to be significant determinants of survival. Adriamycin did not appear to benefit patients with advanced measurable squamous cell carcinoma of the esophagus. Methotrexate and 5-fluorouracil showed comparable activity and survival, although methotrexate was slightly more toxic.

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

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.