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Patient with advanced adenocarcinoma of the pancreas and no prior chemotherapy were treated on a Phase II trial of mitoxantrone. Doses were adjusted for hepatic dysfunction as defined by bilirubin. Twenty-four patients with a bilirubin less than or equal to 1.5 mg% received mitoxantrone 12 mg/m2 i.v. repeated every three weeks. Myelosuppression in the form of leukopenia was the major toxicity. There were no responses in twenty-four evaluable patients.

Forty-three patients with Stage III or IV squamous cell carcinoma of the head and neck were treated with simultaneous hydroxyurea and bleomycin in four treatment levels and with full-dose radiotherapy. Complete responses ranged from 28 to 50% (P = .47), and complete plus partial responses ranged from 57 to 84% (P = .50), in a total of 33 patients. The primary toxicity was moderate to severe mucositis and minimal leukopenia. Despite good initial response, long-term survival duration was not greater than was that for historical controls.

The Southwest Oncology Group (SWOG) in a randomized trial evaluated 5FU infusions in combination with either Mitomycin-C or Methyl-CCNU in patients with disseminated large bowel cancer. A response rate of 18% was noted on the 5FU-Mitomycin limb as compared to 16% on the Methyl-CCNU arm (p = .39). Median survival for all treated patients was 43 weeks on both arms. Myelosuppression was found to be more significant on the Mitomycin-C arm. Regression analysis demonstrated that performance status, sex, and primary site were significant pretreatment characteristics for predicting survival. The response rates associated with this burdensome method of 5FU administration in combination with either Mitomycin-C or Methyl-CCNU appear to offer little advantage over bolus 5FU alone.

The currently accepted staging system for small cell lung cancer considers patients who present with a pleural effusion as having extensive disease, but no series of such patients has been reported. Between 1974 and 1980, 56 patients with ipsilateral pleural effusion as the only evidence of metastatic spread beyond the primary tumor and regional nodes were placed on three consecutive Southwest Oncology Group studies of chemotherapy and radiation therapy for small cell lung cancer. Effusions were cytology-positive in 24: response rates and survival were not different whether cytology was positive or negative. The overall response rate was 77 percent, with 36 percent who achieved complete response, a result comparable to that for patients with limited disease. The survival of effusion “only” patients did not differ significantly among the studies. Median survival of 54 weeks and survival curve for the effusion “only” group as a whole was identical to that of all patients classed as having limited disease by the usual criteria. Long-term disease-free survival was observed just as commonly: 2/17 patients from the first study have disease-free survival at greater than five years, and overall disease-free survival at greater than two years is 22 percent Performance status does not explain the favorable survival in this subgroup, since only 55 percent of effusion patients were fully ambulatory (comparable to extensive disease patients as a group) and even fully ambulatory patients with extensive disease rarely had disease-free survival greater than two years. Patients with ipsilateral pleural effusion as their only evidence of metastasis should be staged as having limited disease.

The role of surgery in small-cell carcinoma of the lung (SCCL) has been recently re-evaluated. We reviewed the records of 262 patients with limited SCCL on Southwest Oncology Group (SWOG) protocol 7628. Fifteen patients were identified who presented after surgical resection (12 lobectomy, three pneumonectomy). All patients were subsequently treated with chemotherapy, radiotherapy +/- immunotherapy (BCG). Median survival time was 10.5 months. Median survival time of patients with initial surgical resection was 25 months (P = .004). Forty-five percent of the surgical patients were alive at two years v 13.7% of the nonsurgical patients (P less than .05). A second subgroup of 33 patients was identified with small primary tumors who did not undergo surgical resection. Median survival time in this group was ten months (P = .03). Site of initial relapse was clearly documented in 142 patients. Fifty-six percent of patients not receiving surgery had initial relapse within the chest compared to 13% of patients undergoing surgery (P = .002). Whether the survival benefit identified was caused by or was incidental to surgical resection of the primary lesion remains to be determined in randomized prospective trials of operable candidates.

Two hundred and ninety-eight patients with limited (confined to chest and supraclavicular area, encompassable by a single radiation portal) small cell carcinoma of the lung were entered on Southwest Oncology Group Protocol 7628. Patients were treated with multi-agent chemotherapy and radiation therapy with or without BCG. Radiation therapy quality control analysis, including dosimetric reconstruction and port film review was introduced after the protocol was activated and was retrospectively applied. Patients who were considered major protocol variations had statistically worse survival (40 weeks versus 60 weeks; P = .002), a lesser improvement in response rate after induction chemotherapy (27 versus 48%; P = .05) and a higher chest failure rate (77 versus 55%; P = .047) than evaluable patients. Five patients relapsed in the brain, all associated with chest failure. Quality control is essential in cooperative group studies.

In order to determine the clinical applicability of the in vitro observation of enhanced cytotoxicity of 5-fluorouracil (5-FU) in the presence of excess reduced folates, the Southwest Oncology Group (SWOG) performed a randomized trial evaluating two dose schedules of 5-FU and folinic acid (FA) in 128 patients with metastatic colorectal cancer. Of 125 eligible patients, 62 were randomized to receive bolus FA (200 mg/m2 days 1 through 4) in addition to 5-FU (1,000 mg/m2 days 1 through 4) by continuous four-day infusion (infusion arm), while 63 were randomized to receive bolus FA (200 mg/m2 days 1 through 5) in addition to 5-FU (325 mg/m2 days 1 through 5) by bolus injection (bolus arm). The toxicities of the two schedules differed, with stomatitis being more severe in the infusion arm and leukopenia being more severe in the bolus arm. The response rates and survival data for the two arms are nearly identical. The median survival of patients on the infusion arm is 11.0 months and of patients on the bolus arm, 10.3 months. The infusion arm produced one complete response (CR) and 12 partial responses (PRs), for a major response rate of 21% of eligible patients. The bolus arm produced three CRs and 11 PRs, for a major response rate of 22% of eligible patients. The response rate produced is minimally superior to recent cooperative group studies of colorectal cancer, but the response rate and survival experience are within the range of experience for treatment with 5-FU alone.

The Southwest Oncology Group in a prospective randomized study compared one year of adjuvant combination chemotherapy with continuous CMFVP to two years of intermittent L-PAM in women with operable breast cancer with histologically positive axillary lymph nodes. In fully evaluable patients with a 42-month median and 30-month minimum follow-up, treatment failures have occurred in 26% of 145 receiving CMFVP and 47% of 167 women given L-PAM (P = 0.002). Disease-free survival times were significantly longer with CMFVP than with L-PAM in the following subgroups: premenopausal women (P = 0.002), postmenopausal women (P = 0.002), women with 1-3 involved axillary nodes (P = 0.003), and women with four or more involved axillary nodes (P = 0.002). CMFVP was effective in pre- and postmenopausal women. There is a significant difference in survival in favor of CMFVP compared to L-PAM (P = 0.005). The life table estimates of survival at 42 months are 86% for women on the CMFVP treatment arm and 73% for women on the L-PAM treatment arm. There was no correlation between the interval from mastectomy to onset of chemotherapy (between one and six weeks) and recurrence rates. Acute toxicity with both treatment arms was moderate and reversible. These results show that continuous CMFVP is superior to intermittent L-PAM in decreasing recurrences and increasing survival in both pre- and postmenopausal women with operable breast cancer with histologically involved axillary nodes.

From November 1976 to March 1979 the Southwest Oncology Group treated 298 patients with limited (disease confined to the chest and encompassed by one radiotherapy port) small-cell carcinoma of the lung with combination chemotherapy and radiotherapy with or without BCG immunotherapy. Two induction chemotherapy programs were utilized: (1) cyclophosphamide, vincristine, methotrexate, fluorouracil; or (2) cyclophosphamide, doxorubicin, and vincristine. Patients received 4500 rads of radiation therapy to the bulk primary tumor and 3000 rads to whole brain followed by maintenance chemotherapy. One-half of all the patients were randomized to receive one vial (5 x 10(8)) of high viability Pasteur BCG by scarification technique given on days 8 and 15 of each 21--28 day treatment cycle. Increased granulocytopenia accompanied the addition of BCG immunotherapy. Patients receiving BCG achieved a response rate of 49% vs. those patients not receiving BCG of 44% (P = 0.579). Median response duration was 40 weeks for the BCG arms and 38 weeks for the arms without BCG; survival was no different, 42 weeks for the BCG arms vs. 50 weeks for the arms without BCG. In patients who responded to therapy and survived longer than one year, those who continued to receive BCG therapy demonstrated a slight, yet significant, survival benefit over those patients not receiving BCG (93 weeks vs. 81 weeks, P = 0.03). It appears that BCG immunotherapy has no beneficial effect on response rate, duration of response, or survival in programs using chemotherapy and radiotherapy for control of limited small-cell carcinoma of the lung except in this small group of long-term survivors.

Clorozotocin was evaluated in patients with advanced colorectal cancer at 225 mg/m2 every six weeks in 14 patients with no prior treatment, at 200 mg/m2 in 43 patients with normal tolerance of prior chemotherapy, and at 100 mg/m2 in 38 patients with extensive or poorly tolerated prior therapy. Median survival for the respective groups was 192, 107 and 79 days; these differences are best explained as a function of performance status. Partial response was reported for one patient, 15 had disease stabilization and two had improvement short of partial remission. Myelotoxicity was acceptable at all doses, with thrombocytopenia being dose limiting at 225 mg/m2. Four patients developed azotemia during or after chlorozotocin treatment. Chlorozotocin has minimal activity against colorectal carcinomas and no dose-response relationship is evident.

The Southwest Oncology Group (SWOG) colorectal adjuvant study 7510 went through two phases. From 1975 to 1977, 309 patients were randomized to chemotherapy alone or the same chemotherapy plus immunotherapy. From 1977 until 1980, 317 patients were randomized among the same two therapy programs and a control group. With a minimum follow-up in either phase of greater than 7 years, data are now mature. They show no difference in relapse-free survival (RFS) nor overall survival (OS) in either the two-way phase or in the three-way phase. There is no indication, except possibly in one very small subset, that the addition of immunotherapy to chemotherapy provides an improvement in OS or in RFS. Using data from patients accrued after randomization to the control group, we fail to find evidence that either chemotherapy alone or chemoimmunotherapy improves OS or RFS when contrasted to outcomes obtained by patients on the control arm. In fact, we have significant evidence, at the P = .016 level, that chemotherapy does not improve OS by at least 50%; we also have significant evidence, at the P = .011 level, that chemoimmunotherapy will not improve OS by at least 25%. No evidence of efficacy was demonstrated for either treatment regimen, even though enough therapy was given to result in significant toxicities. Acute toxicity was at least moderate, but not fatal, in 75% of patients. Recognizable delayed toxicity included rare cases of fatal renal failure and acute leukemia.

Eighty-four previously untreated patients with metastatic adenocarcinoma of the large intestine received intravenous ftorafur at a dosage of 2.25 g/m2/day for 5 consecutive days. Courses were repeated every three weeks. Regressions were noted in 9 of 84 treated patients (11%). Median survival for all patients was 32 weeks. Responders survived only 5 weeks longer than nonresponders; 36 vs. 31 weeks. Central nervous system toxicity was a limiting factor occurring in one-third of patients. Ftorafur in a daily ×5 schedule appears not to make a significant contribution to the management of disseminated colorectal cancer.

A randomized trial was conducted by the Southwest Oncology Group (SWOG) in advanced carcinoma of the stomach and pancreas. Patients were assigned to receive monthly 5-fluorouracil 96-hour continuous infusions with either bolus mitomycin-C or oral methyl-CCNU. Mitomycin-C and methyl-CCNU were administered every eight weeks. The 5 FU-mitomycin combination produced a 14% and 22% response rate in disseminated stomach and pancreatic carcinoma, respectively. The combination of infusion 5 FU and methyl-CCNU achieved responses in 9% and 5% of stomach and pancreatic tumors, respectively. There was ho significant difference in survival between limbs for either tumor. Median survival in gastric carcinoma on the 5 FU-mitomycin regimen was 25 weeks vs. 18 weeks on the 5 FU-methyl-CCNU arm. In pancreatic carcinoma median survival on the mitomycin limb was 19 weeks as compared to 17 weeks on the methyl-CCNU program. Leukopenia was greater for the first course on the mitomycin limb. Regression analysis demonstrated that performance status was the most important pretreatment characteristic for predicting survival in both tumors. Neither 5 FU infusion combination appears to significantly alter the dismal prognosis of advanced upper gastrointestinal neoplasms.

Four cases of cicatricial ectropion secondary to prolonged systemic administration of 5-fluorouracil are described. In 1 patient ectropion resolved with conservative treatment and discontinuation of 5-FU. Another patient developed the ectropion terminally and died before its resolution. In 2 patients surgical repair of the ectropion was unsuccessful in relieving conjunctival symptoms while 5-FU was continued. With prolonged adjuvant chemotherapy programs utilizing 5-FU, this complication may be seen with increasing frequency. Conservative management should be attempted, and patients with this problem should be reassured that symptoms will resolve when 5-FU is stopped.

One hundred sixteen eligible patients with metastatic cancer to the brain were randomized to receive either radiotherapy 3000 rad/ 10 fractions (treatment 1) or the same radiotherapy plus metronidazole 6 gm/m2 (treatment 2). One hundred eleven patients were either fully or partially evaluable. The response rates (CR + PR) and survival showed no significant differences between treatments. Treatment 1: CR + PR 24%, median survival 14 weeks, Treatment 2: CR + PR 27%, median survival 12 weeks. There were no differences observed in response rates based on primary tumor site, neurologic performance status, or extent of metastatic disease. Metronidazole therapy was associated with substantial nausea and vomiting but no neurotoxicity was observed. Oral metronidazole given every other day during radiation therapy provided no clinical benefit for patients with brain metastases compared to radiotherapy alone.

Ninety patients with solid tumors or lymphomas were immunized with a polyvalent pneumococcal vaccine. Pre- and postimmunization antibody titers were determined by radioimmunoassay. Treated patients with lymphoma had poor antibody response whether on or off chemotherapy. Patient with chronic lymphocytic leukemia had the lowest antibody titers of all patients groups. Patients with solid tumors had antibody responses which were similar to those of the control population. Those patients who received sequential chemotherapy and immunization had a tendency for higher postimmunization titers than those patients who received simultaneous chemotherapy and immunization, but the difference was not significant. This study suggests that patients with solid tumors would be expected to benefit from pneumococcal immunization, whereas patients with lymphoma immunized after receiving treatment initially would not be expected to develop protective antibody levels. Recovery of antibody formation in patients with non-Hodgkin lymphoma, which may occur in patients with Hodgkin disease, remains to be determined.

Seventeen patients with islet cell carcinoma received chlorozotocin (CTZ). Nine received 200 mg/m2 IV every 6 weeks and 8 received 100 mg/m2. Responses were seen in eight (2 complete, 5 partial, 1 minor) of 13 patients who had received no prior chemotherapy, and in zero of four who had received prior chemotherapy. Toxicity was mild in most patients and consisted predominantly in myelosuppressions; however, in one patient severe renal failure developed. CTZ may have activity comparable to streptozotocin in this group of patients.

AZQ, an alkylating agent with lipophilic characteristics allowing CNS penetration was studied in patients with primary CNS malignancies refractory to surgical and radiotherapeutic modalities. Responses were evaluated by three criteria: neurologic examination, performance status and CT scan of the brain. Improvement in all three parameters with stable or decreasing doses of decadron was required for a partial response. Thirty-six poor risk (prior chematherapy) patients with Grades III and IV astrocytomas were treated with 30 mg/m2. Three patients had a partial response (14, 17, 60 weeks duration). Two patients had mixed responses (worsening of one disease parameter with improvement in another), four had stable disease and one patient had improvement in neurologic parameters with a stable CT scan. Twenty-six patients had increasing disease. Fifteen good risk patients (no prior chemotherapy) with recurrent grades III and IV astrocytomas were treated at a dose of 40 mg/m2 intravenously every three weeks. There were no objective responses in this group of patients. Three patients with nonastrocytomas were treated and no responses observed. The drug was well tolerated. Myelosuppression in the form of leukopenia and thrombocytopenia was the major toxicity. Myelosuppression required dose reductions in eight patients and discontinuation of therapy due to repeated treatment delays in two patients. AZQ at doses of 30 and 40 mg/m2 given on an intermittent bolus schedule is inactive in patients with Grades III and IV recurrent astrocytoma.

Excerpt To the editor: Johnson and colleagues (1) pointed out, in their recent review article, the indications and contraindications of immunosuppressive therapy for the treatment of rheumatoid art...