Platinol (CDDP) and continuous intravenous infusion 5-fluorouracil in refractory stage IV breast cancer: a phase II study.

Twenty-four patients with refractory Stage IV breast cancer were treated with platinol (100 mg/m2 i.v. Day 1) and 5-fluorouracil (1000 mg/m2 as a continuous infusion over 24 h daily for 5 days). Objective responses occurred in 12 of 24 patients (50%). The median duration of response was 4.9 months. Platinol and 5-fluorouracil in combination are active agents in patients with refractory breast cancer, and clinical trials are warranted in previously untreated patients.

High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer.

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.

Breast conserving surgery and definitive irradiation for early stage breast cancer.

Breast conserving surgery and postoperative breast radiotherapy were used to treat 219 cases of AJCC Stage I and II breast carcinoma at the Michael Reese and University of Chicago Hospitals. Most patients were treated with lumpectomy and axillary sampling followed by breast irradiation to a dose of 46 Gy followed by a boost dose of 14-16 Gy to the surgical bed. The 5-year actuarial local control is 92%. Follow-up is 1 to 10 years and the median follow-up is 36 months. Of the seven patients who recurred in the breast, three failed in the boost site and three failed adjacent to the boost site. The seventh patient recurred diffusely in the breast and skin. Four of the seven recurrences were in patients with positive surgical margins. The 5-year actuarial relapse-free survival is 80%. Factors which had an adverse affect on the cosmetic results were a scar length greater than 8 cm and a volume of resected breast tissue greater than 100 cm3. Treatment related complications were minor and infrequent. Breast conserving surgery followed by radiation therapy is effective in achieving local control with good to excellent cosmetic results.

Radiation therapy for pathologic stage III Hodgkin's disease with and without chemotherapy.

Ninety-eight patients with pathological Stage (PS) III Hodgkin's disease treated between 1969 and 1984 were retrospectively analyzed. Treatment consisted of radiation therapy (RT) alone in 46 patients and combined radiation therapy and chemotherapy (CMT) in 52 patients. The median follow-up was 10 years (range 3-19 years). Fifteen-year year survival for patients with Stage III1-is better than for Stage III2 patients (82% vs 53%; p = .014). Patients with Stage III1A have a favorable prognosis regardless of treatment modality. The probability of freedom from relapse at 15 years for patients with pathological Stage III1A treated with radiation therapy is 70%, compared to 83% for pathological Stage III1A patients treated with combined modality therapy (p = .56). In patients with pathological Stage III2A, III1B, and III2B relapses were less frequent with the use of combined modality therapy compared to radiation therapy. We conclude that pathological Stage III1A patients may be treated with radiation therapy alone; the other subsets of patients benefit from combined radiation and chemotherapy.

Extended mantle radiation therapy for pathologic stage I and II Hodgkin's disease.

Between 1968 and 1983, 135 patients with pathologic stage (PS) I and II Hodgkin's disease were treated with extended mantle radiation technique (EMRT) at Michael Reese Hospital and the University of Chicago Center for Radiation Therapy. EMRT combines both standard mantle and para-aorta fields (M-PA) in one port. Actuarial disease-free survival at 5 and 10 years was 82.5%. Actuarial overall survival was 96% and 83% at 5 and 10 years, respectively. Acute complications were evaluated in 112 patients available for analysis. Severe nausea and vomiting occurred in 13%, weight loss of greater than 10% of body weight in 19%, and acute hematologic toxicity in 4% of patients. Bone marrow suppression was transient and did not interfere with subsequent delivery of salvage treatment with either chemotherapy or radiation therapy in 22 patients who relapsed. The cost of EMRT is 40% lower than the cost of treatment with M-PA. The median treatment time was 38 days, 33% less than the 56 days for M-PA field assuming no interruptions. These results suggest that the EMT is a safe and effective treatment tolerated by most patients. The advantages of this method are eliminating the possibility of technical error of matching between mantle and para-aortic field, decreasing overall treatment time, and reducing the cost.

A 10-year experience with combined modality therapy for stage III small cell lung carcinoma.

During the past 10 years, 240 patients with Stage III small cell lung carcinoma (SCLC) were treated with one of five chemotherapy programs plus thoracic irradiation. In addition, prophylactic cranial irradiation was administered concurrently with thoracic irradiation to 194 patients receiving CAML-HC, VCAM, or MOCA. Seventy-two patients had disease confined to the chest (Stage IIIM0), 30 patients had disease in the chest plus ipsilateral supraclavicular nodal involvement (Stage IIIM0SCN+), and 138 patients had distant metastatic disease (Stage IIIM1); the median survivals were 15.2 months, 12.6 months, and 8.4 months, respectively. The overall complete response rate was 30% and the overall response rate (complete and partial) was 76%. The overall response rates by stage were 86% for Stage IIIM0, 90% for Stage IIIM0SCN+, and 67% for Stage IIIM1. Eight patients (3%) were alive and free of disease at 24 months. Due to continued disease relapse in this group (four of eight patients), long-term survivors should not be identified for a minimum of 3.5 years from the time of initial therapy. Prophylactic cranial irradiation (PCI) effectively reduced the incidence of central nervous system (CNS) relapse in patients with a complete response to therapy (44% relapse without PCI versus 13% relapse with PCI, P less than 0.01). More effective chemotherapy is required for the successful treatment and improved long-term survival of patients with SCLC.

Treatment of soft tissue sarcoma with fibroblast interferon (beta-interferon): an American Cancer Society/Illinois Cancer Council Study.

Twenty patients with soft tissue sarcoma were treated with iv human fibroblast interferon (beta-interferon). Each cycle of treatment involved 5 X 10(6) units over 10 minutes, then 5 X 10(6) units iv over 3 hours daily X 10 with cycles repeated every 20 days X 3. Maintenance therapy was given twice weekly if disease was stable or responsive after three therapy periods. One patient had a partial response to treatment and six patients experienced stable disease for variable periods of time. Toxicity (fever, fatigue, leukopenia, hepatic enzyme elevations) was moderate and tolerable; therapy (except in one case of profound granulocytopenia) was neither interrupted nor discontinued because of toxicity. We conclude that beta-interferon in the dose and schedule used has limited value for soft tissue sarcoma.

Combined modality therapy for Stage IIIMO non-small cell lung cancer. A five-year experience.

Between 1975 and 1980, 101 patients with inoperable Stage IIIMO non-small cell lung carcinoma were entered into combined radiotherapy and chemotherapy trials at Michael Reese Hospital and University of Chicago Hospital. Sixty-four percent of the patients responded. Median survival for all patients was 8.8 months. Responders survived 13.7 months and nonresponders 4.6 months (P = 0.002). Patients treated with 4200 rad had a higher response rate than those treated with 3000 rad (74% versus 54%, P = 0.04) but there was no difference in survival. Although all patients with squamous cell carcinoma died by 30 months, 18% of patients with adenocarcinoma and 20% of patients with large cell carcinoma are long-term survivors. Brain metastases occurred more frequently in patients with large cell or adenocarcinoma than in patients with squamous cell carcinoma (P = 0.02). The prognostic effect of age, initial performance status, sex, histology, and tumor extent are examined. Toxicity was substantial with a 13% treatment-related mortality. Combined modality therapy may benefit selected patients with non-squamous cell types, but more effective chemotherapeutic agents are needed. Prophylactic cranial irradiation in patients with large cell carcinoma or adenocarcinoma may decrease the incidence of subsequent brain metastases.

Response to secondary therapy in patients with adenocarcinoma of the breast previously treated with adjuvant chemotherapy.

The response to secondary therapy, chemotherapy or hormonal, is examined in 26 patients with adenocarcinoma of breast who failed adjuvant chemotherapy. Response rates to tamoxifen or combination chemotherapy, cyclophosphamide, methotrexate, and 5-FU (CMF) or Adriamycin and vincristine (AV) were similar to response rates reported for Stage IV patients, never exposed to cytotoxic agents. Survivals in these 26 patients were similar to those reported for Stage IV patients never exposed to cytotoxics. It is concluded that adjuvant chemotherapy does not lessen future response to secondary therapies or decrease survival.

Multimodality therapy of stage III adenocarcinoma of the breast.

The results of a pilot multimodality program (surgery + radiotherapy + chemotherapy) are reported in 34 women with advanced stage III and IV adenocarcinoma of the breast. The median relapse-free survival for all patients was 24 months, with 74% of the premenopausal patients and 37% of the postmenopausal alive at five years (P = 0.18). The relapse rate was significantly lower in premenopausal patients when compared to the postmenopausal subgroup. Estrogen receptor status was not predictive for relapse or survival.

Acute nephrotoxicity following cis-dichlorodiammine-platinum.

The effects of a single dose of cis-diamminedichloroplatinum (DDP) on the kidney function were investigated in 14 patients with disseminated malignancy and normal renal function. A single dose of DDP (30-50 mg/m2) caused severe proximal tubular dysfunction with increased urinary losses of calcium, magnesium, and amino acids. Phosphate excretion was not affected. DDP can cause proximal tubular dysfunction and close attention must be paid to serum calcium and magnesium levels.

Prognostic factors in patients with non-small cell bronchogenic carcinoma and brain metastases.

Prognostic factors were examined in 38 patients with nonsmall cell lung carcinoma and brain metastases. The most important factors were the response to total therapy (corticosteroids, radiotherapy, and chemotherapy) and the presence of brain metastases alone; these factors had the most impact on survival. Age, sex, histologic type of lung cancer, and initial performance status were not prognostically important. Our results indicate that certain subgroups of patients with nonsmall cell lung carcinoma and brain metastases have a favorable prognosis and should be treated aggressively.

Prognostic value of the estrogen receptor level in pathologic stage I and II adenocarcinoma of the breast.

The relationship between estrogen receptor levels and recurrence of breast cancer was examined in 302 patients with adenocarcinoma of the breast, pathologic stage (PS) I and II. All 117 patients with PS II adenocarcinoma of the breast received adjunctive chemotherapy. In this series, there was no association between the estrogen receptor level and recurrence in either the 185 patients with PS I adenocarcinoma of the breast or the 117 patients with PS II adenocarcinoma of the breast. The most important prognostic variable was the presence or absence of axillary metastases.

Melphalan, vincristine, and 5-FU in advanced colonic carcinoma: results of a pilot study.

The results of treatment with melphalan, vincristine, and 5-FU (MVF) in 32 patients with advanced colonic carcinoma are reported. The objective response rate among 31 patients with measurable disease was 16% (five patients responded). The projected survival for all 32 patients was 277 days. Patients with objective response to MVF had a projected survival of 314 days, significantly longer than the survival of patients with no response to therapy, 84 days (P = 0.01). While toxic effects were mild with MVF, this regimen appears to have greater activity in advanced colonic carcinoma than therapy with 5-FU alone or in combination with nitrosoureas.

Treatment of primary breast cancer with chemotherapy and tamoxifen.

We studied the possibility that the addition of tamoxifen to L-phenylalanine mustard combined with 5-fluorouracil enhances the benefit from the latter two drugs that has been observed in women with primary breast cancer and positive axillary nodes. Recurrence of disease was reduced at two years in patients given the three-drug regimen whose tumor estrogen-receptor levels were greater than or equal to 10 fmol. Among patients greater than or equal to 50 years old treatment failure was significantly reduced (P less than 0.001): by 51 per cent in those with one to three positive nodes and by 64 per cent in those with four or more. Higher receptor levels were associated with a greater probability of disease-free survival. Patients less than or equal to 49 years old were less responsive: those with one to three positive nodes received no benefit from tamoxifen at any receptor level, whereas those with four or more appeared to have reduced treatment failure associated with higher receptor levels. This adjuvant chemotherapy is not indicated in patients less than or equal to 49 years old whose tumor receptor levels are below 10 fmol; there is a suggestion of benefit in patients greater than or equal to 50 years old whose levels are low.

Intracavitary bleomycin for the control of malignant effusions.

The results of treatment with intracavitary bleomycin are reported in twenty patients with a malignant pleural effusion and five patients with malignant ascites. The control rate was 17/20 (85%) patients with malignant pleural effusions and 3/5 (60%) patients with malignant ascites. Toxicities were minimal with fever being the most common side effect in four patients (16%. Bleomycin is an effective and nontoxic sclerosing agent.

Small-cell carcinoma of the lung: a five-year experience with combined modality therapy.

In the past five years, we have treated 89 patients with small-cell carcinoma of the lung with radiotherapy plus one of three chemotherapy programs. The 24 patients with disease confined to the chest (Stage IIIMO) had an 87% response rate to the combined modalities (79% complete responses) and a median survival of 18 months; 13 patients with disease confined to the chest and ipsilateral supraclavicular nodes (Stage IIIMOSCN +) had an 84% response rate (69% complete responses) and 11-month median survival; the 52 patients with distant metastases (Stage IIIMI) had a 71% response rate (15% complete responses) and eight-month median survival. Survival was not affected by adding prophylactic cranial irradiation to the latest regimen, although the CNS relapse rate was reduced. We conclude that our three chemotherapy programs to date differ very little in their effect on survival of patients with metastatic disease. New and more vigorous approaches, possibly including surgery, need to be tested for the management of disease confined to the chest. The designation of patients as Stage IIIMOSCN + is valid because such patients have better survival rates than patients with distant metastatic disease.

Postirradiation malignant fibrous histiocytoma of the lung. Demonstration of alpha 1-antitrypsin-like material in neoplastic cells.

A metastasizing fibrous histiocytoma arising in the lung of a patient who received radiation therapy and long-term chemotherapy for malignant lymphoma is presented. Ultrastructural studies revealed fibroblast-like and histiocyte-like cells, cells of intermediate type showing ultrastructural features of both fibroblast-like and histiocyte-like cells, primitive mesenchymal cells, multinucleate tumor cells, and xanthomatous cells. The neoplastic cells showed dilated rough endoplasmic reticula with intracisternal accumulation of electron-dense material forming lattice-like structures. Direct immunofluorescence staining of the neoplastic cells using antihuman alpha 1-antitrypsin showed specific activity, with fluorescent deposits exhibiting interlacing globular formations. These findings and their implications are discussed.

The predictive value of serial bone scans in assessing response to chemotherapy in advanced breast cancer.

A retrospective analysis was made of 25 patients with breast cancer treated only with chemotherapy in order to determine the predictive value of technetium-99m bone scanning in determining response to chemotherapy. Whole-body scanning demonstrated bone healing in only 3 of 25 patients. However, the presence of stable disease on bone scan correlated with a good prognosis as 12 patients with stable scans had a significantly longer survival time than did the 13 patients who showed progression on scans (17.7 and 7.8 months, respectively P less than 0.01 greater than 0.005, Wilcoxan). Our analysis indicates that bone scans are a relatively crude technique for monitoring response to chemotherapy in patients with breast cancer.