Phase I trial of parenteral 6-thioguanine given on 5 consecutive days.

For almost 30 years, 6-thioguanine (6-TG) has been administered p.o. for treatment of various human cancers, especially leukemias, even though the systemic availability of the drug given p.o. is known to be low and highly variable. Parenterally administered 6-TG has been studied in detail in humans only on a single-day intermittent schedule, although multiple-day intermittent schedules are known to produce maximal cytotoxic effects in several animal species. To develop a multiple-day regimen for parenteral 6-TG therapy, we carried out a dose-seeking and pharmacokinetic study of the drug given i.v. daily for 5 days in patients with various refractory advanced solid tumors. Dose-limiting myelosuppression without other significant toxicity occurred at 55-65 mg/m2 daily for 5 days. After i.v. administration at 65 mg/m2, the mean peak plasma concentration of 6-TG ranged from 6-10 microM. These concentrations are 8-300 times greater than peak plasma concentrations of 6-TG in plasma reported to occur after p.o. administration at 100 mg/m2. We suggest that the antitumor activity of 6-TG be reassessed against human cancers in regimens of i.v. administration on multiple-day intermittent schedules.

Phase I study of recombinant leukocyte A human interferon combined with BCNU in selected patients with advanced cancer.

Interferons manifest diverse immunomodulatory and antiproliferative characteristics. Since their spectrum of toxicities includes primarily fatigue and anorexia rather than the myelosuppression concomitant with cytotoxic therapies, it is conceptually appealing to combine both modalities. We conducted a phase I trial among 18 patients using the combination of leukocyte A recombinant interferon (IFN-rA) and BCNU. The intramuscular (IM) IFN-rA dose for the initial 12 patients was 12 X 10(6) U/m2 three times a week for an anticipated duration of 12 weeks. Among these patients, we escalated the monthly intravenous (IV) BCNU dose from 50 mg/m2 to 150 mg/m2. Six subsequent patients received IFN-rA 12 X 10(6) U/m2, days 1 to 3, and BCNU 150 mg IV on day 3 of each monthly cycle. Dose-limiting toxicities from both regimens were fatigue and myelosuppression. We recognize the limitation of small sample sizes. Nevertheless, in the absence of a significant number of life-threatening toxicities, it appears that near maximal doses of BCNU and concomitant IFN-rA can be administered with safety in an outpatient setting.

Pilot study of a continuous five-day intravenous infusion of etoposide concomitant with cisplatin in selected patients with advanced cancer.

In view of experimental and clinical data suggesting enhanced antiproliferative efficacy from a continuous infusion of etoposide (VP-16) concomitant with cisplatin (CDDP), we performed a dose-seeking study of a five-day infusion of VP-16, 30 mg/m2/24 h and CDDP, 18.5 to 25 mg/m2/24 h. Among eight patients with advanced solid tumors, dose-limiting toxicities were leukopenia and thrombocytopenia. There were no clinically significant renal, neurologic, or otologic sequelae. Nausea and vomiting were mild and transient. Although the trial was not designed as a phase II assessment, we observed three objective regressions among three patients with advanced gastric adenocarcinoma who had failed prior chemotherapy. The total CDDP dose is similar to five-day single agent studies, yet the total VP-16 dose is approximately 24% to 50% less than a five-day single agent VP-16 dose. The recommended regimen for continuous 120-hour infusion is VP-16, 30 mg/m2/24 h and CDDP, 20 mg/m2/24 h, repeated at monthly intervals.

Phase II study of recombinant leukocyte A interferon (IFN-rA) plus cimetidine in disseminated malignant melanoma.

Thirty-five eligible patients with disseminated malignant melanoma received intramuscular recombinant leukocyte interferon (IFN-rA), 50 X 10(6) U/m2 three times weekly (TIW) for an intended duration of 12 weeks concomitant with daily oral cimetidine, 1,200 mg/d in four divided doses. For all study participants, the median survival time was six months. Among 21 "good risk" patients (performance score [PS] 0, 1 and no prior chemotherapy), we observed seven partial regressions (33%). Six patients had stability of disease (29%), seven had immediate disease progression, and one discontinued treatment after two doses without tumor evaluation due to side effects. Times to disease progression of five patients with regressions of soft-tissue disease were 2.1, 3.3, 3.5, 3.7, and 4.3 months. Two patients had partial regressions of lung nodules for 2.0 and 3.8 months. We observed one regression among 14 "poor risk" patients (PS 2, 3, or prior chemotherapy). A 46-year-old woman with prior treatment had a partial regression of soft-tissue disease for 4.1 months. Four "poor risk" patients achieved disease stability, and nine progressed immediately. Leukopenia (WBC count less than 4,100/microL) affected 21 (66%) of 32 patients with WBC count data. The median count was 3,100/microL; range, 1,300 to 8,400/microL. We detected two cases of mild thrombocytopenia (100,000 and 120,000/microL). Other noteworthy toxicities included moderate-to-severe nausea (34%), anorexia (63%), and fatigue (80%). All patients experienced myalgias. Twenty patients had dosage decreases during the first cycle, and 14 of the 16 patients remaining on study after the first cycle required dosage reductions. The overall response rate is similar to our prior studies with IFN-rA as a single agent using TIW doses of 50 X 10(6) U/m2 and 12 X 10(6) U/m2 among 31 and 30 patients, respectively.

Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma.

PURPOSE: We conducted a randomized prospective trial in selected patients with fully resected high-risk stage I and II malignant melanoma. PATIENTS AND METHODS: Interferon alfa-2a (IFN-alpha 2a) 20 x 10(6) U/m2 was administered three times each week for 12 weeks by the intramuscular route. Both the treatment group (n = 131) and the control group (n = 131) were evenly balanced with regard to relevant prognostic discriminants. RESULTS: The median disease-free survival (DFS) time was 2.4 years for the IFN-alpha 2a group and 2.0 years for the observation group (log-rank P = 0.19). The median survival times were 6.6 years for IFN-alpha 2a and 5.0 years for observation (log-rank P = .40). For stage I patients (n = 102), there was no apparent therapeutic advantage from IFN-alpha 2a therapy. The DFS for stage II patients was a median of 10.8 months in the control group versus 17 months in the treatment group. The overall survival time was 4.1 years for the treatment group versus 2.7 years for the control group. The differences in DFS for stage II patient were significant in a Cox model. These results must be interpreted cautiously because of subset analysis. A severe flu-like toxicity occurred in 44% of patients, 13% lost at least 10% of their baseline weight, and 45% experienced a worsening of Eastern Cooperative Oncology Group (ECOG) performance score. CONCLUSION: Our findings indicate trends that suggest a possible benefit for selected patients with high-risk malignant melanoma. The results will require further study in a larger patient population for confirmation.

Randomized trial of tamoxifen alone or combined with aminoglutethimide and hydrocortisone in women with metastatic breast cancer.

A randomized clinical trial was performed to compare the efficacy of tamoxifen (TAM) alone with that of TAM plus aminoglutethimide (AG) and hydrocortisone (HC). Patients failing TAM could receive AG and HC. Objective responses to therapy were seen in 21 of 49 TAM patients (43%) and 25 of 51 TAM, AG and HC patients (49%). Time to disease progression and survival distributions were not significantly different between the treatment arms. Toxicity was greater for patients treated with TAM, AG, and HC and the trial was discontinued early for this reason. Twenty-four patients received AG and HC after TAM therapy and three (12%) achieved a response. We conclude that the combination of TAM, AG, and HC is not recommended over TAM alone because toxicity appears to outweigh any potential therapeutic advantage.

Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma.

We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-aspartate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.

A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer.

One hundred eight eligible patients with advanced, metastatic non-small-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, and cisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (sequential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete non-cross resistance.

Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma.

Thirty patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 12 X 10(6) U/m2, three times weekly for a planned treatment duration of three months. This dose was selected in view of our prior phase II data indicating that 50 X 10(6) U/m2 three times weekly produced excessive toxicity. In this current trial we observed three objective partial regressions (20%) among the 15 better-risk patients (performance score 0, 1, and no prior chemotherapy) with times to disease progression of 1.9, 9.6, and 12.9+ months. There were also three regressions (one complete and two partial) among the 15 poor-risk patients (performance score 2, 3, or prior chemotherapy) with progression times of 3, 3.2, and 9.6+ months. For all patients, the median survival time was 4.2 months. One half of the patients were observed to have progressive disease within one month of commencing treatment. Responding metastatic lesions were limited to soft tissue, although one patient also had a partial response of a lung nodule. The most substantial toxicities were moderate-to-severe myalgias (27%), nausea (33%), anorexia (47%), and fatigue (50%). Among the 22 patients with weight loss, the median was 2.3 kg (range, 0.6 to 8.4 kg). Hematologic and hepatic toxicity was transient and of little clinical significance. Our study indicates that rIFN-alpha A in the dose and schedule that we used is clinically tolerable and has antitumor activity in malignant melanoma. The response rate was similar to results observed in our previous study of a higher dose regimen.

A controlled pilot study of high-dose methotrexate as postsurgical adjuvant treatment for primary osteosarcoma.

Thirty-eight patients whose primary extremity or limb girdle osteosarcomas had been completely excised (37 amputations, one limb sparing procedure) were allocated at random to two treatment groups receiving respectively regular follow-up examinations plus a high-dose methotrexate (HDMTX) regimen or regular follow-up without primary adjuvant chemotherapy. Although the vincristine, HDMTX, leucovorin regimen was generally quite tolerable when given at three-week intervals for one year and most of the chemotherapy patients followed the planned HDMTX dose escalations from 3 to 6 to 7.5 g/m2, delayed methotrexate excretion limited dosage escalations in 25%. An estimated 52% of the 38 patients were surviving five years after randomization and an estimated 42% remained continuously relapse-free after five years. No significant differences between the outcomes of the 20 treated and the 18 untreated patients were apparent; however, power to detect differences was low. Furthermore, no significant differences in postmetastasis survival were apparent between the 12 treated and 10 untreated patients who relapsed. Approximately 20% of these failing patients appear to have been salvaged for long-term survival. This pilot study of HDMTX confirms the continuing need for controlled clinical trials in determining the therapeutic value of adjuvant chemotherapy programs for patients with primary osteosarcoma.

A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer.

We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.

Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy.

PURPOSE: This analysis was performed to determine the most appropriate volume that should be encompassed by thoracic radiation treatments (TRTs) for patients with limited-stage small-cell lung cancer (LSSCLC) who have responded to initial chemotherapy. PATIENTS AND METHODS: A retrospective review of all patients (N = 67) with LSSCLC who were not entered onto a research protocol and were treated at our institution between the years of 1982 and 1990 was performed. Fifty-nine of 67 patients had adequate information regarding the size of the tumor before the start of chemotherapy (computed tomographic [CT] scan of chest or chest x-ray), the size of the tumor before TRT, and the TRT field size based on a simulation radiography. All 59 patients were treated with cyclophosphamide-based chemotherapy, and TRT was generally delivered concomitantly with chemotherapy following two to three cycles of chemotherapy alone. RESULTS: Of 59 patients, 28 were treated with TRT field sizes that encompassed postchemotherapy tumor volumes, and 31 patients were treated with TRT field sizes that encompassed prechemotherapy tumor volumes (defined as a volume that included at least a 1.5-cm margin on the prechemotherapy tumor volume). Nineteen patients had an intrathoracic recurrence of disease as the first site of recurrent small-cell carcinoma: 10 of 31 patients treated with TRT fields that encompassed prechemotherapy tumor volumes and nine of 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes. For the 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes, the greatest distance that the prechemotherapy tumor volume (without margins) extended beyond the edge of the TRT field was 0.5 to 5.0 cm, with a median of 2.5 cm. All 19 of the intrathoracic recurrences were in-field failures, although two patients (one prechemotherapy volume and one postchemotherapy volume) did have concurrent pleural effusions. CONCLUSION: These results indicate that the use of TRT fields that encompass postchemotherapy tumor volumes does not increase the risk of marginal failures or intrathoracic failures outside the TRT field.

A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.

We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.

Phase III clinical trial of the combination of cisplatin, dacarbazine, and carmustine with or without tamoxifen in patients with advanced malignant melanoma.

PURPOSE: A prospective randomized phase III clinical trial was conducted to assess whether the addition of tamoxifen (TAM) to the three-agent regimen of cisplatin (CDDP), dacarbazine (DTIC), and carmustine (BCNU) significantly increased the progression-free survival and overall survival of patients with advanced malignant melanoma. PATIENTS AND METHODS: Patients with advanced malignant melanoma were treated with CDDP + DTIC + BCNU (CDB) with or without TAM. The dose schedule was CDDP 25 mg/m(2) given intravenously (IV) for 30 to 45 minutes in 500 mL of dextrose and (1/2) normal saline (NS) on days 1 to 3 of a 3-week cycle; DTIC 220 mg/m(2) IV for 1 hour in 500 mL of dextrose and (1/2) NaCl on days 1 to 3 of a 3-week cycle; BCNU 150 mg/m(2) IV for 2 to 3 hours in 750 to 1,000 mL of dextrose and 5% water on day 1 of every odd 3-week cycle; and TAM 20 mg taken orally every morning. RESULTS: There were 184 eligible patients enrolled. These patients were observed until death or for a minimum of 1.3 years. At last contact, 12 were still alive. The median time to progression was 3.4 months on the CDB arm and 3.1 months on the CDB + TAM arm. The median survival time was 6.8 months with CDB and 6.9 months with CDB + TAM. Progression-free survival (P =.429) and overall survival (P =.545) were not found to differ by treatment. CONCLUSION: The addition of TAM to this three-agent regimen of CDB was not found to provide a meaningful clinical advantage in the treatment of patients with advanced malignant melanoma.

Disseminated malignant melanoma and recombinant interferon: analysis of seven consecutive phase II investigations.

We have performed seven phase II trials with recombinant interferons (IFN) involving 191 patients with biopsy-proved, measurable disseminated malignant melanoma. The regimens and numbers of patients have included IFN-alpha 2A, 50 X 10(6) U/m2 subcutaneous (SQ) TIW (regimen A, 31 patients); IFN-alpha 2A, 12 X 10(6) U/m2 SQ TIW (regimen B, 30 patients); IFN-alpha 2A with cimetidine as an immunorestorative agent (regimen C, 35 patients); IFN-gamma (regimen E, 29 patients); IFN-alpha 2A with IFN gamma (Regimen E, 20 patients); IFN-alpha 2A with bis-chloroethylnitrosourea (BCNU) (regimen F, 30 patients); and IFN-alpha 2A with the biochemical modulator, difluoromethylornithine (DFMO) (regimen G, 16 patients). The objective regression rates were as follows: A, 23%; B, 20%; C, 23%; D, 10%; E, 5%; F, 7%; G, 0%. Despite the higher response rate from regimen A, there appeared to be no survival advantage from any of these programs. The median time to progression was 1 month with a median survival time of 6 months. Most regressions involved soft tissue disease, were partial, and occurred within 2-3 months of treatment. Four patients received IFN for approximately 6 months and have manifested extraordinarily durable regressions of greater than 4+ years. The alpha-regimens produced a flu-type illness and anorexia which were dose-related. Leukopenia was most noteworthy with regimens containing gamma-interferon. Ongoing trials involving alternative and improved immune-related modalities are awaited with keen interest.

Malignant melanoma: cost and reimbursement issues.

Once malignant melanoma has spread below the epidermis and metastasized, the response rate to conventional therapy is relatively poor. Investigational drug programs currently are exploring a number of promising treatment options, including biologic therapy (alpha interferon and interleukin-2) and immunotherapy. However, the costs of investigational drug therapy are high, and there are signs that the federal government and third-party payers are increasingly reluctant to reimburse patient expenses for participation in clinical drug trials. Unless financial support for investigational therapy is maintained, conventional therapy with low rates of cure will continue to be reimbursed while the use of state-of-the-art research drugs will slow to a halt.

Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer.

PURPOSE: Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population. METHODS AND MATERIALS: Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease. RESULTS: Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively. CONCLUSION: Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting.

Results of combination chemotherapy and thoracic radiation therapy for unresectable non-small cell carcinoma of the lung.

From October 1979 to December 1982, 126 patients with locally advanced unresectable or inoperable Stage II (7 patients), Stage IIIA (81 patients), and Stage IIIB (38 patients) non-small cell carcinoma of the lung were treated in a prospective randomized trial using five cycles of CAP (Cytoxan, Adriamycin, and cisplatin), T-CAP (triazinate plus CAP), or V-CAP (VP-16 plus CAP) chemotherapy with thoracic radiation therapy (TRT). TRT consisted of 40 Gy in 10 fractions (split-course) with cycles 3 and 4 of chemotherapy. The treatment field included the primary tumor, ipsilateral hilum, mediastinum, and ipsilateral supraclavicular fossa. All patients were followed until death or for a minimum of 5 years for survivors. The evaluable subgroup consisted of 102 patients who completed TRT. Median and 5-year survivals for the entire group were 14.0 months and 10%, respectively; for the evaluable subgroup, they were 14.8 months and 12%, respectively. There was a trend toward better survival with V-CAP plus TRT than with CAP plus TRT (p = 0.08). Median and 5-year survivals were 16.2 months and 18%, respectively, with V-CAP plus TRT. Of eight prognostic variables analyzed for their association with survival, only Eastern Cooperative Oncology Group performance status (0,1 versus 2) (p = 0.02) and weight loss (less than or equal to 10% versus greater than 10%) (p = 0.05) were significant. Sex, age, T stage, N stage, overall stage, and histologic type were not significantly associated with survival. Failure analysis revealed 83 patients (81%) with identifiable first failures. The median time to first failure was 9.8 months, and the median survival after first failure was 4.7 months. Failure patterns included local failure alone (19%), local and distant (20%), and distant alone (43%). Nineteen percent of patients had no documented progression. Total failure patterns were local in 39% and distant in 63%. Twenty-three patients (23%) had failure in the brain; they accounted for 31% of all distant failures. In 20 of these patients (20% of all patients), this was the only site of failure. There were eight (8%) initial nodal failures in 96 untreated contralateral supraclavicular fossae. No initial failures were seen in any of 101 untreated contralateral hila. The data suggest the following: (a) Combined treatment with V-CAP and TRT yielded excellent results (median survival, 16.2 months; 5-year survival, 18%).(ABSTRACT TRUNCATED AT 400 WORDS)

Psychosocial issues in oncologic practice.

Impressive gains in the survival of some patients with malignant diseases have primarily reflected the availability of multimodality programs for selected pediatric neoplasms and germ cell tumors and for subsets of patients with regional breast cancer, colorectal cancer, and small-cell lung cancer. Most patients with advanced solid tumors, however, will die of their disease. Sophisticated psychosocial investigations of patients with advanced cancer have targeted several areas in which clinicians can positively influence quality of life. Families often "cascade through an avalanche" of emotional upheavals as patients struggle with the sequelae of their illness. After a patient dies, clinicians should be familiar with some generally recognized patterns of behavior that are indicative of a normal mourning process. This knowledge may help clinicians be aware of situations that might necessitate intervention of other professionals, either medical or pastoral. Attention to psychosocial events is an integral part of a comprehensive oncologic program to facilitate patients and families to live in an atmosphere of peace and dignity.

Malignant melanoma: an emerging and preventable medical catastrophe.

The natural history of malignant melanoma, including the diagnosis, prognosis, and treatment options, is reviewed in an attempt to formulate appropriate management strategies. Awareness on the part of clinicians is important, inasmuch as early detection of malignant melanoma offers the best chance for improved survival. Most lesions are excised with a margin of 1 to 3 cm, and follow-up assessment intervals are based on the depth of the primary lesion. Follow-up usually consists of a medical history, physical examination, chest roentgenography, and hematologic and chemistry profiles. Routine use of sophisticated imaging studies is unnecessary because the yield from such an approach has been low. Patients with melanomas thicker than 1.6 mm and those with histologic evidence of involvement of regional lymph nodes are at risk for development of disseminated disease and may be candidates for adjuvant therapy. In patients with severe weight loss and poor nutrition because of advanced disease, analgesic agents, stool softeners, and appetite enhancers are palliative measures that should be considered.