Seminom im klinischen Stadium I

Context

Stage I seminoma is the most commonly diagnosed testicular cancer and has an excellent prognosis. Independent of whether adjuvant treatment or active surveillance strategy is applied up to 100?% of patients can be cured.

Material and methods

Research of literature and analysis of clinical trials.

Results

The recurrence rate for stage I seminoma is approximately 15?%. A retrospective analysis identified invasion of the rete testis and a tumor size of >?4 cm as prognostic risk factors; however, not all recent studies could confirm these findings. Relapse risk can be reduced to 4–5?% when adjuvant treatment with either single dose carboplatin area under the curve of 7 (AUC 7) or radiotherapy (para-aortic field with 20 Gy) is applied. However, this leads to overtreatment in 85?% of cases and there is concern about long-term toxicity.

Conclusions

Active surveillance therefore represents the preferred treatment option for the majority of patients with stage I seminoma according to most international guidelines. An optimal follow-up schedule based on published recommendations should be applied to avoid unnecessary exposure to ionizing radiation and to ensure patient compliance.     

Stereotaktische Strahlentherapie im Stadium I des nichtkleinzelligen Lungenkarzinoms

For patients with inoperable stage I non-small cell lung cancer (NSCLC) stereotactic body radiotherapy (SBRT) has evolved as the standard of care. As a non-invasive method, SBRT has led to a significant progress with high local control rates regularly amounting to nearly 90% and a high disease-specific (actuarial) survival after 5 years of approximately 75%. The application of SBRT has now been widely adopted in many radiation units; however, its use places high demands on the technical apparative equipment and a sophisticated quality assurance in the individual centers. The choice of appropriate fractionation schemes depends primarily on the distinction between a central and a peripheral tumor location. With appropriately adjusted dose regimens very good treatment tolerance can be achieved. In comparison to sublobar resection for patients with advanced chronic obstructive pulmonary disease (COPD, GOLD III or IV), SBRT is superior in terms of post-interventional morbidity and mortality. For the operable stage I the results of SBRT treatment in small collectives are as effective as those of patients who received a guideline-conform lobar resection. This is the conclusion of the analysis of two prospective randomized trials, which were terminated early; however, clinical evidence is still limited in this context. Promising currently running clinical trials are examining the application of SBRT as a boost after chemoradiotherapy in stage III NSCLC and also the combination of SBRT and immunotherapeutic approaches in stage I.     

Chirurgische Therapie im Stadium I und II des nichtkleinzelligen Lungenkarzinoms

Background

Despite modern diagnostics and multimodal treatment strategies, overall survival of lung cancer could not be significantly improved in recent decades. The majority of patients with non-small cell lung cancer (NSCLC) have distant metastases at the time of diagnosis (57%) and only approximately 40% of patients are in a potentially curable tumor stage.

Material and methods

A systematic literature search concerning original research and review articles on surgery of NSCLC in stages I and II was carried out in the PubMed database.

Results

For patients in an early tumor stage, stages I and II tumors according to the 8th edition of the Union for International Cancer Control (UICC) tumor stage classification, surgical removal of the tumor remains the therapeutic gold standard. By complete anatomical resection (lobectomy, bilobectomy or pneumonectomy) combined with a systematic mediastinal and hilar lymphadenectomy, 5?year survival rates of more than 80% in early stage IA and 48% in stage II can be achieved. In addition to open surgical resection, video-assisted, minimally invasive thoracoscopic (VATS) resection was successfully implemented worldwide for the treatment of NSCLC patients in stages I and II. For patients with stage II NSCLC, adjuvant chemotherapy was shown to improve the overall survival.

Discussion

Whether targeted therapies or immunotherapy in a neoadjuvant or adjuvant treatment modality further improve the survival of NSCLC patients in the multimodal treatment of early stage NSCLC, is currently under investigation in randomized studies.

     

Primärtherapie des Hodentumors und Prognosefaktoren nichtseminomatöser Keimzelltumoren im klinischen Stadium I

Die Primärdiagnostik bei Verdacht auf einen testikulären Keimzelltumor umfasst die Sonographie von Hoden und Retroperitoneum, die radiologische Stagingdiagnostik mittels CT von Abdomen und Thorax sowie die Bestimmung der Tumormarker AFP,-hCG und LDH. Die Primärtherapie des unilateralen Hodentumors besteht in der inguinalen Ablatio testis; metachrone Zweittumoren oder Tumoren in einem Solitärhoden können durch die Organ erhaltende Tumorenukleation behandelt werden. Die kontralaterale Hodenbiopsie zum Nachweis einer testikulären intraepithelialen Neoplasie (TIN) kann fakultativ erfolgen, die Standardtherapie der TIN besteht in der lokalen Radiatio mit 18 Gy. Im klinischen Stadium I nichtseminomatöser Keimzelltumoren existieren mit der Surveillance, der primären Nerv schonenden retroperitonealen Lymphadenektomie und der primären Chemotherapie 3 konkurrierende Therapiealternativen mit gleich hoher Heilungsrate bei unterschiedlichem Nebenwirkungsspektrum. Bei einer Heilungsrate von 98% muss im Vordergrund der therapeutischen Bemühungen die langfristige Aufrechterhaltung der Lebensqualität stehen, sodass klinisch und individuell nutzbare Prognosefaktoren wünschenswert wären, die eine Vorhersage okkulter retroperitonealer Metastasen erlauben. Auf dem Boden jüngster prospektiver Studien der German Testicular Cancer Study Group stellen der fehlende Nachweis einer vaskulären Invasion und ein niedriger Proliferationsindex (MIB- 1-Expression <70%) mit einem positiven Vorhersagewert von 86% reproduzierbare Risikofaktoren für die Definition einer Niedrigrisikogruppe und der Möglichkeit einer Surveillance-Strategie dar. Eine Hochrisikogruppe kann auf dem Boden histopathologischer oder molekularer Marker nicht definiert werden; es empfiehlt sich die Nerv schonende RPLA oder die primäre Chemotherapie.     

Prim?rtherapie des Hodentumors und Prognosefaktoren nichtseminomat?ser Keimzelltumoren im klinischen Stadium I

Die Primärdiagnostik bei Verdacht auf einen testikulären Keimzelltumor umfasst die Sonographie von Hoden und Retroperitoneum, die radiologische Stagingdiagnostik mittels CT von Abdomen und Thorax sowie die Bestimmung der Tumormarker AFP,-hCG und LDH. Die Primärtherapie des unilateralen Hodentumors besteht in der inguinalen Ablatio testis; metachrone Zweittumoren oder Tumoren in einem Solitärhoden können durch die Organ erhaltende Tumorenukleation behandelt werden. Die kontralaterale Hodenbiopsie zum Nachweis einer testikulären intraepithelialen Neoplasie (TIN) kann fakultativ erfolgen, die Standardtherapie der TIN besteht in der lokalen Radiatio mit 18 Gy. Im klinischen Stadium I nichtseminomatöser Keimzelltumoren existieren mit der Surveillance, der primären Nerv schonenden retroperitonealen Lymphadenektomie und der primären Chemotherapie 3 konkurrierende Therapiealternativen mit gleich hoher Heilungsrate bei unterschiedlichem Nebenwirkungsspektrum. Bei einer Heilungsrate von 98% muss im Vordergrund der therapeutischen Bemühungen die langfristige Aufrechterhaltung der Lebensqualität stehen, sodass klinisch und individuell nutzbare Prognosefaktoren wünschenswert wären, die eine Vorhersage okkulter retroperitonealer Metastasen erlauben. Auf dem Boden jüngster prospektiver Studien der German Testicular Cancer Study Group stellen der fehlende Nachweis einer vaskulären Invasion und ein niedriger Proliferationsindex (MIB- 1-Expression <70%) mit einem positiven Vorhersagewert von 86% reproduzierbare Risikofaktoren für die Definition einer Niedrigrisikogruppe und der Möglichkeit einer Surveillance-Strategie dar. Eine Hochrisikogruppe kann auf dem Boden histopathologischer oder molekularer Marker nicht definiert werden; es empfiehlt sich die Nerv schonende RPLA oder die primäre Chemotherapie.     

Therapie im Stadium IV des nichtkleinzelligen Lungenkarzinoms mit Treibermutation

Background

Systemic treatment of non-small cell lung cancer (NSCLC) is currently undergoing a paradigmatic change with impressive dynamics. Patients with advanced disease are treated based on the analysis of biomarkers either with immunotherapy, a combination of immunotherapy with chemotherapy or with driver mutation-directed targeted drugs. Treatment of acquired resistance remains a particular challenge. An increasing knowledge of the molecular mechanisms underlying resistance enables the development of more potent inhibitors.

Objective

This review focuses on the state of the art and current developments in targeted therapy of advanced stage NSCLC.

Material and methods

This review is based on the summary and interpretation of publications on preclinical and clinical studies in the field of targeted treatment of advanced NSCLC.

Results and conclusion

Targeted treatments against activating mutations in the EGFR and BRAF genes as well as ALK and ROS1 fusions define the standard first line treatment for approximately 15?% of patients with advanced NSCLC. In retrospective analyses this development has led to a substantially prolonged overall survival in these subgroups. Targeted therapies against further aberrations are in clinical evaluation and a targeted treatment is currently available for approximately 30% of patients. Next generation inhibitors are characterized by a high effectiveness against tumors with acquired resistance to tyrosine kinase inhibitors (TKI) and improved tolerability and are increasingly being used as first line treatment. In order to understand the molecular causes and to select the most effective treatment, rebiopsies play a special role in resistance.

     

Aktueller Stand der Diagnostik und Therapie des nichtkleinzelligen Lungenkarzinoms (NSCLC) im Stadium III

Based on the considerable heterogeneity of patient subgroups in stage III non-small-cell lung cancer (NSCLC)—despite the slightly more differentiated 8th edition of the Union Internationale Contre le Cancer (UICC)/International Association for the Study of Lung Cancer (IASLC) staging classification—increasingly individualized treatment of these patients has become necessary. Initial interdisciplinary assessment of potential operability is a key factor for treatment selection. Standard treatment for the majority of stage III NSCLC patients is still concurrent chemoradiotherapy. However, based on the equivocal and clinically relevant positive results of the phase III PACIFIC trial, this treatment should be followed by consolidation therapy with durvalumab for 12 months in patients with proven PD-L1 expression in the tumor. In patients who are evaluated as potentially operable in interdisciplinary consensus, multimodality treatment protocols including definitive surgical resection of the tumor are still standard. Based on the positive data on immunotherapy in inoperable patients, there are now multiple interesting scenarios for integration of this new modality into the treatment of patients with localized disease, which should be carefully analyzed in well-designed prospective clinical trials.     

Suizidalität im klinischen Kontext hämatopoetischer Stammzelltransplantationen

Background

Allogeneic hematopoietic stem cell transplantation (HSCT) is nowadays implemented as a standard treatment in hematological oncology. In a few years there are expected to be 500,000 long-term survivors of HSCT worldwide and the numbers will show a clear increase. Little is known about suicidal ideation and suicide in the context of HSCT.

Objective

The current state of knowledge on suicide after HSCT was systematically reviewed. Specific and as yet unresolved issues are presented.

Material and methods

A systematic literature search on the topics of HSCT and suicide was carried out in the Medline and Embase databases. The results are discussed in detail.

Results

Only seven articles were found that address the topic of suicide and suicidal ideations after HSCT. In two publications the topic is only mentioned without any further analysis. In one case report important indications of specific risk factors within the HSCT setting are presented.

Conclusion

There is an alarming paucity of investigations on suicide after HSCT. The existing publications indicate a twofold increase of the risk of suicide for patients who had to undergo a HSCT. Younger men with somatic and/or psychological stress are particularly at risk The suicide risk is elevated for many years after therapy; therefore, an ongoing screening of long-term survivors is recommended. There is a substantial lack of specialized knowledge on suicide after HSCT. Furthermore, case reports suggest a deleterious impairment of communication in the context of HSCT. Practical advice as part of a proactive suicide prevention is discussed in this article.

     

Therapiemöglichkeiten des Seminoms im klinischen Stadium I und II unter Berücksichtigung der Langzeittoxizität

Die Onkologie - Bei mehr als 80 % aller Patienten mit einem Seminom wird die Diagnose im Stadium&nbsp;I–IIB gestellt. In den letzten Jahrzehnten wurden Therapiealgorithmen anhand...     

A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days

Purpose Perillyl alcohol (POH) has been shown to have both chemopreventative and chemotherapeutic activities in preclinical studies. The underlying mechanism(s) of action of POH have yet to be delineated but may involve effects on the transforming growth factor (TGF) and/or the Ras signaling pathways. A phase I study of POH for 14 days out of every 28 days in subjects with advanced malignancies was performed to evaluate dose escalation, toxicity, pharmacokinetics, and effects on TGF and Ras.Methods POH was administered orally (500 mg capsules containing 250 mg POH) to 20 patients four times a day on a continuous basis for 14 days followed by a 14-day rest period, for up to three courses. The starting dose was 1200 mg/m² per dose. A minimum of three patients were treated and evaluated at each escalating POH dose. Pharmacokinetic analysis was performed on days 1 and 14 of course 1 and day 1 of selected later courses. Plasma TGF levels were measured on days 1 and 14. Peripheral blood lymphocyte (PBLs) Ras levels were assayed on days 1 and 2 of the first course.Results The 20 patients, of whom 15 were evaluable, received doses between 1200 and 2000 mg/m² per dose for a total of 43 courses. The most common observed toxicities were nausea, gastrointestinal distress, and fatigue. Other toxicities included diarrhea or constipation, hypokalemia, and one incidence of acute pancreatitis. Due to these toxicities, four of the patients declined further treatment either during or after the second course. While POH was not detected in plasma, perillic acid (PA) and dihydroperillic acid (DHPA) were detected in plasma, and the peak levels at 2000 mg/m² per dose were approximately 600 M (PA) and 50 M (DHPA). There was some evidence for linearity in the peak plasma levels and area under the concentration–time curve of the metabolites from the starting dose to the highest dose. Metabolite pharmacokinetics were not significantly affected by ingestion in the fed or fasting state, or repeated exposure to POH. No evidence for an effect of POH on plasma TGF or PBL Ras protein was observed. No objective responses were observed.Conclusions In adults with advanced malignancies, an interrupted administration schedule of POH did not reveal significant advantages over continuous dosing schedules.     

Zervixkarzinom und seine Vorstufen

Background

The nomenclature of squamous and glandular precursor lesions has been reformed in the World Health Organization (WHO) classification as well as in national and international guidelines in recent years.

Methods

This study was based on a PubMed search and a review of current national and international guidelines pertaining to the subject.

Results

With regards to cervical intraepithelial neoplasia associated with human papillomavirus (HPV), an accurate distinction between low grade and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively) and a thorough evaluation of glandular precursor lesions are emphasized. Morphological changes associated with the productive phase of HPV infection are referred to as LSIL and changes associated with deregulation of HPV expression and of the cell cycle as HSIL; however, for the clinical management of squamous cell precursor lesions, the 3?tiered classification of cervical intraepithelial neoplasia (CIN) is still indispensable. In the differential diagnosis of HPV-associated precursors and metaplastic squamous cell and glandular lesions in particular, the relevance of p16 immunohistochemistry or combined p16/Ki-67 determination is emphasized. The staging of cervical cancer has been complemented by subdividing stage IIA into IIA1 and IIA2 and the importance of a standardized determination of morphological prognostic factors is underlined. Particular attention must be paid to differentiate special types of squamous cell carcinoma and rare non-HPV associated adenocarcinomas.

Conclusion

The recently updated recommendations and guidelines on the diagnosis and classification of cervical cancer have taken our improved understanding of the biology and natural history of the disease into account.

     

Phase I study of an oral formulation of irinotecan administered daily for 14 days every 3 weeks in patients with advanced solid tumours

A phase I study was conducted with oral irinotecan given daily for 14 days every 3 weeks in 45 patients with solid tumours to establish the maximum tolerated dose (MTD), toxicity, preliminary antitumour response and pharmacokinetics. Irinotecan was administered orally as a powder-filled capsule at doses ranging from 7.5 to 40 mg/m² per day. Tumours were predominantly colorectal (30) together with 10 other gastrointestinal, 2 breast, 2 small cell lung and 1 ovarian. All but three patients had received prior chemotherapy. The median number of administered cycles was 3 (range 1–19). Gastrointestinal toxicities (grade 3 nausea, grade 3/4 vomiting and diarrhoea) and one incidence of grade 3 asthenia were dose limiting. There were no grade 3/4 haematological toxicities. The MTD was 30 mg/m² per day. There were two documented partial responses, one in a patient with cancer of the small intestine and the other in a patient with colon cancer. Stable disease was seen in 16 patients (35.5%). Peak concentrations of irinotecan and metabolite SN-38 were reached within 2.0–2.4 h. The metabolic ratio of SN-38 AUC to irinotecan AUC was 0.17±0.10 (mean±SD). The dose recommended for phase II studies is 30 mg/m² per day administered daily for 14 days every 3 weeks.     

Bewältigungsstrategien in der Onkologie

Background

Coping with cancer is a great challenge for patients and their relatives. The initial shock of the diagnosis is followed by different coping strategies and phases of adaptation and processing of the situation.

Methods

This article is based on a selective literature search in PubMed on the topic of coping with disease and cancer.

Results and discussion

Psychosocial resources and factors of resilience can heIp patients to find positive perspectives apart from all the negative aspects associated with cancer. Coping with denial requires a sensitive handling by professionals bearing in mind the protective character of this coping strategy for the mental state of patients. Confrontation with reality is only a realistic option if denial results in damaging effects. Aggression and depression are antagonists in disease processing and coping strategies and are often in danger of becoming unbalanced. It must be taken into consideration that a reactive depressive mood might be an adequate state, whereas a depressive episode should be differentiated as a mental comorbidity that needs to be treated.

     

Phase I dose-escalation study of oral vinflunine administered once daily for 6 weeks every 8 weeks in patients with advanced/metastatic solid tumours

Purpose

Vinflunine ditartrate is a microtubule inhibitor belonging to the vinca alkaloid family. This phase I study was carried out to evaluate the maximal tolerated dose, the safety profile, the pharmacokinetics and the activity of oral vinflunine (VFL) given daily in patients with advanced/metastatic solid tumours and who have failed standard therapy.

Methods

Patients were treated with oral VFL administered once daily for 6 weeks followed by a two-week rest. Sequential dose-escalating cohorts of patients were enrolled into 5 dose levels: 20, 40, 60, 75 and 95 mg/day.

Results

In total, 27 patients received 53 cycles. Dose-limiting toxicities (DLT) were observed from 60 mg/day. The dose levels 75 and 95 mg/day were both assessed as maximal tolerated dose. The most frequent dose-limiting toxicities were of haematological origin. The recommended dose was defined as 60 mg/day, dose at which 4 patients experienced long stabilizations (≥4 months) and also received longer treatment duration in comparison with the other dose levels. Blood exposure of VFL and its active metabolite 4-O-deacetyl vinflunine (DVFL) increased proportionally to the dose levels. The concentrations of VFL and DVFL reached a steady state at, respectively, 5 and 20 days and remained stable for the rest of the cycle. Increased incidence of DLT/SAE was consistent with the increase of VFL dose and drug exposure.

Conclusions

These results showed the feasibility of daily oral vinflunine administration on a 6-week treatment duration. This new schedule of administrations enabled sustained and stable blood concentrations of both VFL and DVFL. The recommended dose was defined at 60 mg/day, dose at which 4 patients experienced clinical benefit.     

Phase I and pharmacokinetic study of edotecarin, a novel topoisomerase I inhibitor, administered once every 3 weeks in patients with solid tumors

Purpose: Edotecarin (J-107088) is a potent indolocarbazole topoisomerase I inhibitor which is structurally distinct from the camptothecins. This study aimed to determine the maximum tolerated dose (MTD), the recommended dose for future Phase II studies and the safety, pharmacokinetic profile, and preliminary antitumor activity of edotecarin in a population of patients with advanced solid tumors. Experimental design: Edotecarin was administered as a single dose by IV infusion over 2 h every 21 days (with 1 week permitted for recovery from toxicities, if needed) in patients with advanced solid tumors. Doses ranged from 8 to 15 mg/m². Pharmacokinetic assessments were performed during and after the first administration. Results: Twenty-four patients received 61 cycles of therapy. Dose-limiting toxicities (infection, febrile neutropenia, constipation, ileus, and prolonged grade 4 granulocytopenia) were observed in 3 of 5 evaluable patients at the 15 mg/m² dose, defining the MTD. The most commonly reported non-hematologic toxicities were anorexia, nausea, malaise, and constipation. Diarrhea was neither frequent nor severe. Neutropenia was the most common hematologic toxicity (grade 3–4 in 21/23 patients during cycle 1). Plasma concentrations of edotecarin rose rapidly following the start of the 2-hour infusion, reaching C _max values of 103±17 ng/ml at the 13 mg/m² dose, and decreased steeply after the end of the infusion. Plasma concentrations declined to approximately 1–2 ng/ml at 26 h post start of infusion, the last PK sampling time point. The mean apparent plasma half-life of the drug was 20 h, which should be considered a preliminary estimate until results from studies with a longer duration of plasma sampling are available. A mean of 1.4–3.6% of the dose was recovered as unchanged drug in the urine over 48 h. Unconfirmed tumor regression ≥50% was observed in 2 patients, 1 with metastatic gastric carcinoma and 1 with esophageal cancer. Conclusions: The MTD of edotecarin administered IV over 2 h every 21 days was 15 mg/m². The recommended dose for Phase II studies with a 3-week schedule (with 1 week permitted for recovery from toxicities, if needed) is 13 mg/m². The observed safety profile and preliminary evidence of antitumor activity warrant further investigation of this drug in solid tumors.Presented at the American Society of Clinical Oncology 2002 Annual Meeting (abstract no. 385).     

Phase I and pharmacokinetic study of anhydrovinblastine every 3 weeks in patients with refractory solid tumors

PURPOSE: Anhydrovinblastine (AVLB) is a novel semisynthetic vinca alkaloid. We conducted a phase I trial to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT) and pharmacokinetics of AVLB given as a 1-h intravenous infusion once every 3 weeks in patients with advanced refractory solid tumors. PATIENTS AND METHODS: Entered into the study were 24 patients with normal bone marrow, hepatic and renal function, and of these 21 were evaluable. There were 12 males and 12 females with a median age of 60 years (range 27-75 years). Diagnoses were non-small-cell lung cancer (NSCLC) (11), colorectal cancer (5), soft tissue sarcoma (4), and miscellaneous (4). Patients had had a median of three prior chemotherapy regimens (range one to six). A total of 51 courses were administered at doses of 2.5, 5, 10, 16.5, 21, 25 and 30 mg/m(2) in one, three, one, three, six, six and one patient respectively. RESULTS: Grade 2 infusional hypertension, anemia, and dizziness were noted at 16.5 mg/m(2). At 25 mg/m(2), two of six evaluable patients had DLT. DLT was grade 4 constipation, neutropenia and grade 3 nausea/vomiting. At 21 mg/m(2) one of six evaluable patients had DLT (grade 3 nausea/vomiting). This dose was the MTD. Stable disease was noted in one patient with metastatic sarcoma to the lungs and in three patients with metastatic NSCLC. The pharmacokinetics of AVLB were linear, and well characterized by a two-compartment model, with a mean clearance of 26.4 l/h per m(2) and median terminal half-life of 18 h. CONCLUSIONS: The recommended phase II dose is 21 mg/m(2). A phase II study in NSCLC is being initiated.     

Phase I trial of PEG-interferon and recombinant IL-2 in patients with metastatic renal cell carcinoma

PURPOSE: Pegylated interferon alpha-2b (PEG-Intron) is a conjugate of polyethylene glycol (PEG) and interferon alpha-2b, has a prolonged half-life, and an increased area under the curve (AUC) for interferon alpha-2b. The combination of PEG-Intron with recombinant interleukin-2 (rIL-2) was investigated in a phase 1 trial. To determine the maximal tolerable dose (MTD) and preliminary efficacy of concurrent subcutaneous (SC) administration of PEG-Intron and rIL-2 in patients with metastatic renal cell carcinoma (RCC). METHODS: Cohorts of 3-6 patients received escalating doses of PEG-Intron (I-1.5, II- 1.5, III-3.0, IV-3.0, V-4.5 microg/kg SC) given weekly in combination with rIL-2 administered three times weekly (TIW) for 6 weeks. rIL-2 dose levels were escalated in weeks 1 and 4 (I-10.0, II-15.0, III-15.0, IV-20.0, V-20.0 MIU/m(2) SC), and 5.0 MIU/m(2) SC TIW was administered during weeks 2, 3, 5 and 6. RESULTS: Thirty-four patients (24 men; 10 women) were accrued at dose levels I (n = 4), II (n = 4), III (n = 6), IV (n = 14), and V (n = 6) between October 2000 and October 2002. All but one patient had prior nephrectomy (n = 33) and all but one patient (97%) had received no prior systemic therapy. Patients received a median of four cycles of treatment (range 1-9). Dose limiting toxicity occurred at dose level V and included grade 4 neutropenia and hypoxemia. A partial response was found in 5 pts (15%). Median progression-free and overall survival were 9.0 (95% C.I. 5.6-13.1 months) and 31.9 months (95% C.I. 17.2-61.9 months), respectively. CONCLUSION: The combination of PEG-Interferon and SC rIL-2 can be administered with acceptable toxicity.