Robert B. Livingston

Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study.

The Southwest Oncology Group entered 453 patients with extensive small cell carcinoma into a combined modality treatment program, involving a randomized comparison of three different chemotherapy regimens for remission induction, and of maintenance chemotherapy alone versus maintenance treatment with cycles of reinduction added at six and 12 months. In addition, there was systematic comparison of diagnosis by institutional pathologist versus review panel pathologist. No difference was observed among the three different induction arms with respect to the incidence of response to treatment (61%), complete response (16%), or survival duration (median, 31 weeks). Neither overall response rate nor survival are superior to previous results. However, patients who achieved a complete response demonstrated significant survival benefit if they were in the group who received reinduction chemotherapy, as opposed to maintenance alone. This observation may apply most importantly to patients with small cell lung cancer of limited extent, for whom complete response is achieved in a majority. Agreement of institutional and review panel pathologists on the diagnosis of small cell lung cancer was observed in 94% of reviewed cases. A final observation is that the omission of chest irradiation results in a dramatic increase in the incidence of initial relapse at the primary tumor site. This suggests that future studies will need to use better therapy for local control in responding patients.

Intensive Dose-Dense Compared With High-Dose Adjuvant Chemotherapy for High-Risk Operable Breast Cancer: Southwest Oncology Group/Intergroup Study 9623

PURPOSE Southwest Oncology Group (SWOG)/Intergroup study 9623 was undertaken to compare treatment with an anthracycline-based adjuvant chemotherapy regimen followed by high-dose chemotherapy (HDC) with autologous hematopoietic progenitor cell support (AHPCS) with a modern dose-dense dose-escalated (nonstandard) regimen including both an anthracycline and a taxane. PATIENTS AND METHODS Participants in this phase III randomized study had operable breast cancer involving four or more axillary lymph nodes and had completed mastectomy or breast-conserving surgery. Patients were randomly assigned to receive four cycles of doxorubicin and cyclophosphamide followed by HDC with AHPCS or to receive sequential dose-dense and dose-escalated chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide. The primary end point of this study was disease-free survival (DFS). RESULTS Among 536 eligible patients, there was no significant difference between the two arms for DFS or overall survival (OS). Estimated five-year DFS was 80% (95% CI, 76% to 85%) for dose-dense therapy and 75% (95% CI, 69% to 80%) for transplantation. Estimated 5-year OS was 88% (95% CI, 84% to 92%) for dose-dense therapy and 84% (95% CI, 79% to 88%) for transplantation. CONCLUSION There is no evidence that transplantation was superior to dose-dense dose-escalated therapy. Transplantation was associated with an increase in toxicity and a possibly inferior outcome, although the hazard ratios were not significantly different from 1.

Influence of chest radiotherapy in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A Southwest Oncology Group study

The value of radiotherapy to the chest (RC) in disseminated small cell lung carcinoma (SCLC) has been questioned. Two protocols for disseminated SCLC from the Southwest Oncology Group (SWOG) have been compared. They were developed four years apart. The first one included radiotherapy (RT), 3000 rad in two weeks, to the primary tumor, mediastinum and supraclavicular areas, while the second one deleted any RC. Multidrug chemotherapy (CT) and brain RT were used in both protocols. Nonresponders to CT were removed from the study. Our main findings are as follows: (1) Initial chest relapses (patients with no initial extrathoracic relapse) have increased from 24–55% when RC is not given (P = 0.0001). Overall chest relapse (adding those patients that relapsed simultaneously in the chest plus other sites) in the second protocol was 73%. (2) Amount of response to CT does not influence the chances for relapse. Even complete responders to CT have a high chance for chest relapse. (3) Sites of relapse without RC are mainly in the primary tumor, ipsilateral hilus and mediastinum. (4) With RC, relapses shift to the chest periphery, mostly to the lung outside the radiotherapy field and to the pleura. (5) The two very different CT regimens have produced similar percentages and duration of response. (6) CT schema with periodic reinductions prolongs duration of response and survival over schema with continuous maintenance. Hence, interruption of CT to allow RC does not seem to adversely influence CT efficacy. From our results and the review of the literature we conclude that: (1) patients with disseminated SCLC that respond to CT should be given RC to decrease chest relapses. (2) A dose of 3000 rad in two weeks seems to be enough to produce a low percentage of chest relapse in disseminated SCLC, as survival of these patients is short and many will die prior to developing chest relapse. However, according to the literature, 4000–4800 rad is probably a more effective dose. (3) More studies and guidelines are needed to outline proper boundaries of radiotherapy fields, to decrease chances of peripheral chest relapses. (4) Median survival might not be a good parameter to evaluate the impact of RC in disseminated SCLC. The study of long‐term survivors seems to be more important.

Phase II trial of 5‐fluorouracil, adriamycin, mitomycin C, and streptozotocin (FAM‐S) in pancreatic carcinoma

Twenty‐five patients with unresectable and metastatic pancreatic carcinoma were treated with the combination of 5‐fluorouracil, Adriamycin, mitomycin C and streptozotocin (FAM‐S). Twelve of 25 patients responded (48%) and four patients demonstrated stable disease. Median survival of all patients was 6.75 months, and seven of 25 patients survived more than 12 months. Hematologic toxicity was moderate, and the predominant side effect recorded was nausea and vomiting (80% patients). Combination chemotherapy in pancreatic carcinoma may provide palliation and randomized trials are warranted to confirm these results.

High dose BCNU with autologous bone marrow rescue in the treatment of recurrent malignant gliomas

Eleven patients with malignant gliomas recurring after surgery and radiation therapy, were treated with high dose BCNU 1050-1200 mg/ M2 with autologous bone marrow rescue. Four patients also received concomitant 5-fluorouracil 1000 mg/ M2/24 hr daily for three days. Eight of ten evaluable patients demonstrated improvement on CAT scan as well as a decrease in steroid requirement. All patients surviving longer than two weeks after BCNU administration experienced full hematologic recovery. No delayed myelosuppression was seen after a single course of high dose therapy. Two patients died as a result of therapy, one following a second induction of BCNU for a total cumulative BCNU dose of 2 400 mg/ M2 and one of infection while cytopenic. Additional toxicity includes one steroid-responsive interstitial pneumonitis, one centrilobular necrosis of the liver which spontaneously resolved and one episode of deep vein thrombosis. With limitation on the maximum BCNU dose and distribution of the total dose over three days, high dose BCNU can be administered with acceptable toxicity. This approach may offer a higher response rate than that expected for standard dose BCNU.

VP16-213, cisplatinum, and adriamycin salvage therapy of refractory and/or recurrent nonseminomatous germ cell neoplasms

SummaryEleven patients with recurrent and/or resistant nonseminomatous germinal cell neoplasms refractory to conventional chemotherapy were treated with the combination VP16-213, cis-diamminedichloroplatinum, and adriamycin. One complete response, four partial responses which at surgery were benign teratomas, and six partial responses have been observed. Four patients are prolonged survivors (>18 months). The possibility that this regimen may offer true salvage for refractory patients exists. Incorporation of VP16-213 into initial treatment regimens for germinal cell neoplasms is warranted.

Combination chemotherapy, radiotherapy, and BCG immunotherapy in extensive (metastatic) small cell carcinoma of the lung. A southwest oncology group study

From November 1976 to November 1978, the Southwest Oncology Group treated 254 patients with extensive (metastatic) small cell carcinoma of the lung with combination chemotherapy and radiotherapy with and without BCG immunotherapy. Patients receiving BCG achieved a response rate of 50% versus those patients not receiving BCG of 46% (P = .704). Response duration was 20 weeks for the BCG arms and 23 weeks for the no‐BCG arms; survival was 28 weeks for the BCG arms versus 29 weeks for the no‐BCG arms. An adverse effect in patients surviving more than one year was detected; those continuing to receive BCG had significantly shorter survival, 60 weeks versus 85 weeks (P = .019). Toxicities of the programs were not affected by the addition of BCG immunotherapy. It appears that BCG immunotherapy has no beneficial effect on response rate or duration of response in programs using chemotherapy and radiotherapy for control of metastatic small cell carcinoma of the lung. In addition, because of the adverse effect on long‐term survival, we do not recommend the addition of BCG immunotherapy as a treatment modality in this tumor type.

Colchicine in refractory chronic lymphocytic leukemia. A Southwest Oncology Group study.

SummaryFourteen patients with active chronic lymphocytic leukemia who had failed prior therapy were treated with progressive doses of weekly intravenous colchicine beginning at 2 mg and escalating as high as 7 mg in a single injection. Responses were seen in two of 14, with a lessening of adenopathy and splenomegaly. Toxicity was characterized by gastrointestinal intolerance in eight and thrombocytopenia in 12. There is activity of the drug in chronic lymphocytic leukemia but, as administered in this study, high dose therapy is not ideal and it may be more beneficial if the drug were given as low dose daily or weekly therapy.

Methods to Predict Response to Chemotherapy

There have been numerous attempts to develop an assay system that will allow the correct choice of systemic therapy for an individual patient with cancer. The empirical method used at present to select such therapy involves both the possibility that ineffective agents will be chosen and the probability that the patient will suffer some untoward effects as a result of their use